Response of Peroxisome Proliferator-Activated Receptor Genes and Gamma- Glutamyl Transferase in Rats to High-Intensity Interval Training and Livergol

Response of Peroxisome Proliferator-Activated Receptor Genes and Gamma- Glutamyl Transferase in Rats to High-Intensity Interval Training and Livergol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Response of Peroxisome Proliferator-Activated Receptor Genes and Gamma- Glutamyl Transferase in Rats to High-Intensity Interval Training and Livergol Farah Nameni, Akram Kasiri This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7831368/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 40 You are reading this latest preprint version Abstract Introduction : Obesity is a major health problem and has many clinical consequences on the body's organs. Genetic factors, lifestyle, diet, and physical activity can play an effective role in weight control. Objective : This study aimed to investigate the effect of a period of intense interval training and Livergol supplementation on PPARγ and GGT in obese rats. Methodology : The statistical sample of the present study consisted of 40 male Wistar rats, which, after obesity was induced, were divided into four groups of ten: a control group, an exercise group (intensive interval training), a supplement group (Livergol supplementation), and an interval exercise and Livergol supplementation group. After completing the 8-week exercise and supplementation protocol, samples were collected from the adipose tissue and heart of the rats in the fasting state and on the day after the last exercise session, and then transferred to the reference laboratory. For statistical analysis, mean, standard deviation, Shapiro-Wilk, Levine tests, and two-way analysis of variance were used. If the results were significant, the Bonferroni test was used to determine the changes (P≤0/05). Results : The expression level ofthe PPARγ gene was lower in the control group and the Livergol supplement group, but it increased in the exercise group and the exercise + Livergol group. The activity level of GGT enzymes was higher in the control group than in the Livergol, exercise, and exercise + Livergol supplement groups. Discussion and Conclusion: According to the study's results, it can be concluded that consuming Livergol and engaging in intense interval exercise has been effective in reducing liver damage and enzyme disorders by influencing sugar and fat metabolism and increasing the expression of the PPARγ gene. Additionally, engaging in periodic and intense exercise activities, combined with the consumption of Livergol, may have a positive effect on the regulation of the GGT enzyme. Health sciences/Diseases Health sciences/Gastroenterology Biological sciences/Physiology Livergol high-intensity interval training Proliferator-Activated Receptor Gamma-Glutamyl Transferase Genes Figures Figure 1 Figure 2 Figure 3 Figure 4 Highlights 1. HIIT upregulated PPARα/γ expression, improving lipid metabolism. 2. HIIT enhanced hepatic function, aiding metabolic disorder control. 3. Livergol boosted antioxidant defense and lowered GGT activity. 4. HIIT + Livergol showed synergistic effects on liver genes and enzymes. 1. Introduction Overweight and obesity are major health concerns worldwide and have major epigenetic consequences, such as liver disorders. Fatty liver disease or steatosis is an example of liver cell damage that is influenced by genetic factors, lifestyle, diet, and physical activity status. Multidimensional approaches of nutritional control, weight loss, and exercise may be beneficial ( 1 ). An important training protocol is interval training, which consists of repeated short bouts of exercise with rest periods. In this training, physiological components are subjected to greater stress ( 2 ). Exercise may cause physiological changes in liver fat content and expression of various genes. The use of medicinal plants is also recommended due to fewer side effects. Livergel may also be useful due to its silymarin content in strengthening the immune system, antioxidant effects, and enhancing liver cell regeneration. (2022) investigated the effect of silymarin supplementation on serum IL6 and CRP levels after a single aerobic exercise session in healthy men, which resulted in a reduction in inflammatory markers ( 3 ). Treatment modalities for diseases and the efficacy of drugs effective in treating liver disorders, such as interferon and corticosteroids, although appropriate, have been inconsistent in many cases, and their side effects have been a barrier to prescription. Researchers have extensively studied herbal medicines as an alternative to chemical treatments. In a study by Sobolev et al. (2022), after 4 weeks of silymarin intake by patients, AST and ALT enzyme levels decreased. In animal studies, silymarin has also shown its protective effects against various liver toxins caused by hepatotoxic drugs. Studies have also been conducted on the transcription of peroxisome proliferator-activated receptor (PPARγ) and the molecular function of human factor ( 4 ). The effect of activating PPARγ by GW0742, a specific agonist of this isoform, has also been investigated in mice. They differ in terms of chromosomal location, ligand affinity, target gene expression, and metabolic functions. Their biological functions have been observed in inflammation, obesity, and diabetes. Although exercise interventions have been shown to alter gene expression in some studies, no significant effects have been observed on lipid and aminotransferase profiles ( 5 ). The present study aimed to investigate the efficacy of Livergol in improving liver function and to examine the effects of exercise on GGT and PPARγ in obese rats. Therefore, the question now arises: Does livergol consumption and intense interval training affect the expression of the peroxisome proliferator-activated receptor gamma (PPARγ) gene and the gamma-glutamyl transpeptidase (GGT) enzyme in obese male rats? Research Methodology This research was fundamental and applied, and was conducted experimentally with a post-test design in four groups. The present study was conducted in the form of a two-group experimental design (experimental and control). The research population consisted of male Wistar rats. Accordingly, 50 male rats with an average weight of 246 ± 15 grams were obtained from the Pasteur Laboratory Animal Breeding Center and transferred to the Animal Science Research Laboratory of the university, and were kept in the animal house environment for 1 week in order to adapt to the new conditions. The rats were cared for in transparent polycarbonate cages measuring 30×15×15cm, manufactured by Razi Rad Company, at a temperature of 22 ± 3 degrees. All animal experiments were performed according to the ARRIVE guidelines and were in accordance with the Animal (Scientific Procedures) Act 1986 and related guidelines, the European Union Directive 2010/63 for the protection of animals used for scientific purposes, or the NIH (National Research Council) Guide for the Care and Use of Laboratory Animals. Institutional ethics approval number IR.IAU.VARAMIN.REC.1399.006 was obtained from the Ethics Committee of the Faculty of Medicine, Islamic Azad University, Varamin Pishva Branch. 2. Methods 2 − 1. Experimental Design and Intervention Protocol To induce weight gain and establish a high-calorie dietary model in rats, we employed a hypercaloric diet enriched with fat and simple carbohydrates. The diet was formulated to provide approximately 4.5–5.2 kcal/g, which is considerably higher than the ~ 3 kcal/g of standard chow. Specifically, the macronutrient composition consisted of 40–45% of total energy from fat (derived from sources such as soybean oil, coconut oil, or lard), 35–40% from carbohydrates (a mixture of cornstarch and sucrose), and 15–20% from protein (primarily casein or soy protein). In addition, the diet was supplemented with approximately 5% cellulose as a source of fiber, along with standard mineral and vitamin mixtures according to the AIN-93 formulation. An example formulation, per 100 g of diet, included: 20 g of casein, 25 g of fat, 30 g of cornstarch, 15 g of sucrose, 5 g of cellulose, 2 g of vitamin mixture, and 3 g of mineral mixture( 6 ). This hypercaloric regimen has been shown to significantly promote body weight gain, with male rats typically increasing from approximately 246g to 330-350g within 6–10 weeks of feeding. All animals were weighed once or twice per week throughout the study period using a digital precision balance, and weekly growth curves were plotted for each group. Daily food and water intake were recorded to calculate average energy intake per cage. At the end of the experimental protocol, the Lee index was calculated as an indicator of adiposity and metabolic status using the formula: This diet induced general weight gain and metabolic alterations (increased triglycerides, hepatic steatosis, and insulin resistance).Resting heart rate was measured using a tail-cuff plethysmography system. Prior to recording, the mice were placed in a quiet environment for several minutes to minimize stress and obtain accurate measurements. The behavioral status of the mice was monitored daily and assessed based on parameters such as locomotor activity, self-grooming, responsiveness to environmental stimuli, and signs of stress or lethargy. Each animal was evaluated using a six-point scale, where 6 indicated a highly active and responsive state, and 1 represented lethargy or severe stress. When the weight of the mice increased to 350 ± 20 g, they were divided into four groups of ten, including the exercise group, the livergol group, the exercise + livergol group, and the control group, and familiarization with the laboratory environment and the main exercise protocol began. Thus, the exercise group was exposed to intense interval training for 8 weeks. The supplement group received livergol supplements for 8 weeks. In addition to the supplements, the exercise group underwent intense interval training for 8 weeks, which was accompanied by the consumption of livergol supplements. Livergol tablets were obtained from Goldaru Herbal Pharmaceutical Company (Isfahan, Iran) under a valid health license issued by the General Directorate of Food and Drug Supervision, Ministry of Health (Batch No. LG-2401, Certificate of Analysis No.COA-2024-117). Each Livergol tablet contains 140 mg of standardized milk thistle (Silybum marianum) extract, equivalent to approximately 70–80% silymarin, of which silybin is the major active flavonolignan component( 7 ). For experimental use, tablets were finely powdered and freshly prepared each day by suspending the powder in a 0.5% carboxymethyl cellulose solution as a vehicle. The compound was dissolved at room temperature to achieve the desired concentration, ensuring complete solubility and avoiding precipitation. Freshly prepared solutions were used for each administration. Livergol was administered orally by gavage at a dose of 300 mg/kg body weight, once daily between 8:00 and 9:00 am. The selected dose (300 mg/kg) was based on previous animal studies demonstrating hepatoprotective and antioxidant effects of milk thistle extract without inducing toxicity in rats. After gavage, animals were observed for 3–5 minutes to ensure full ingestion, and only those that had completely swallowed the solution were returned to their home cages. This procedure was performed consistently to guarantee accurate dosing and reliable experimental outcomes ( 8 ). The control and exercise + placebo groups received maltodextrin in the same form so that all four groups were equally exposed to the physiological effects of gavage. A conveyor belt model A1400Y10, Pishro Andisheh Sanat Company, made in Iran, was used in this study. The conveyor belt slope was considered zero in all stages ( 9 ). In the present study, only male Wistar rats were studied to minimize the potential confounding effects of the physiological cycle in females and to avoid the study being affected by fluctuations in estrogen and progesterone levels. Changes in sex hormones can significantly affect metabolic, enzymatic, and gene expression responses. By limiting the study to males, we aimed to reduce biological variability and increase the internal validity of the findings.The control group did not take any supplements and did intense interval training (Table 1 ). Table 1 High-intensity interval training program ( 10 ) Week Odd days (Moderate intensity) Even days (High intensity) Rest between bouts Incline (°) Sessions/week Warm-up / Cool-down Progression 1 2 × 3 min at 40 m/min 3–5 × 30 s at 54 m/min 60 s active rest at 16 m/min 0 5 5 min at 16 m/min (before & after) Start phase 2–3 3 × 3 min at 40 m/min 5–7 × 30 s at 54 m/min 60 s active rest at 16 m/min 0 5 5 min at 16 m/min (before & after) Gradual increase 4–5 4–5 × 3 min at 40 m/min 7–9 × 30 s at 54 m/min 60 s active rest at 16 m/min 0 5 5 min at 16 m/min (before & after) Increased load 6–7 5–6 × 3 min at 40 m/min 9–11 × 30 s at 54 m/min 60 s active rest at 16 m/min 0 5 5 min at 16 m/min (before & after) Near-maximum load 8 6 × 3 min at 40 m/min 15 × 30 s at 54 m/min 60 s active rest at 16 m/min 0 5 5 min at 16 m/min (before & after) Peak phase To eliminate the effects of the training protocol and uncontrollable variables that may have occurred during the exercise, the day after the last training session (24 hours), they were anesthetized by ethical principles and intraperitoneal injection of a combination of ketamine (70 mg/kg) and xylazine (3–5 mg/kg). After dissecting the animals, adipose tissue was removed from the subcutaneous epidermal fat layer of the mice and washed in physiological saline. It was then immediately frozen with liquid nitrogen at a temperature of -80 degrees Celsius and stored for later examination. After the final training session, all animals were euthanized according to ethical standards to minimize pain and distress. Anesthesia was induced by intraperitoneal injection of ketamine (90 mg/kg) and xylazine (10 mg/kg), followed by an overdose of sodium pentobarbital (200 mg/kg, i.p.) for euthanasia. All procedures were conducted in accordance with the institutional guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Ethics Committee (Ethics code: IR.IAU.VARAMIN.REC.1399.006). 2–2.PPARγ gene expression study using the RT-PCR technique 2–2.PPARγ gene expression study using the RT-PCR technique The expression of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) was assessed using reverse transcription quantitative PCR (RT-qPCR). Specific primers for the target gene (PPARγ) and the reference gene (β-actin) were designed using the NCBI database and Primer-BLAST (Table 2 ). Primer design criteria included specificity, melting temperature (Tm ~ 60°C), absence of significant secondary structures, and amplicon size between 100–200 bp. RNA extraction and cDNA synthesis: Total RNA was isolated from tissues using the Qiagen RNA extraction kit (Qiagen, Germany) following the manufacturer’s protocol. RNA quantity and purity were assessed using a Nanodrop spectrophotometer (Thermo Scientific, USA). Only samples with an A260/A280 ratio between 1.8–2.0 were used for cDNA synthesis. Reverse transcription was performed with a Qiagen cDNA synthesis kit according to the manufacturer’s instructions. qPCR amplification qPCR reactions were performed in triplicate using SYBR Green dye on a Real-Time PCR system (Applied Biosystems, USA). Thermal cycling conditions were: initial denaturation at 95°C for 5 min, followed by 35 cycles of 95°C for 30 s, 60°C for 30 s, and 72°C for 30 s, with a final extension at 72°C for 5 min. Validation and quality control: Amplification efficiency for each primer pair was determined by generating standard curves from a 5-fold serial dilution of cDNA; efficiencies ranged between 90–105%. Melt curve analysis was performed at the end of each run to confirm the specificity of amplification, ensuring a single peak per primer pair. Selected PCR products were further validated by agarose gel electrophoresis to confirm the expected product size. The stability of β-actin expression was confirmed across all experimental groups; additionally, a second housekeeping gene (GAPDH) was assessed to ensure normalization reliability. Data analysis Relative gene expression was calculated using the ΔΔCt method. First, the difference in Ct values between the target and reference gene (ΔCt) was determined for each sample. Then, the ΔCt of the intervention groups was compared with the control group to obtain ΔΔCt. Fold change in gene expression was calculated as 2^-ΔΔCt and reported accordingly( 11 ). Table 2 Primer information for examining PPARγ gene expression. Target gene Product size (bp) Tm (°C) Primer sequence (5′→3′) Direction Source / Reference PPARγ 150 60 AGGCCGAGAAGGAGAAGCTG Forward Designed using NCBI Primer-BLAST TGGCCACCTCTTTGCTCTA Reverse Designed using NCBI Primer-BLAST β-actin 120 60 AGAGGGAAATCGTGCGTGAC Forward Designed using NCBI Primer-BLAST CAATAGTGATGACCTGGCCGT Reverse Designed using NCBI Primer-BLAST GAPDH 123 62.6 AGGTCGGTGTGAACGGATTTG Forward PrimerBank ID: 6679937a1 GAPDH 123 60.2 TGTAGACCATGTAGTTGAGGTCA Reverse PrimerBank ID: 6679937a1 2–3.Investigation of GGT Biochemical Index Rats were anesthetized with an intraperitoneal injection of ketamine (80–100 mg/kg body weight) and xylazine (5–10 mg/kg body weight). Following confirmation of deep anesthesia, the abdominal cavity was opened, and the liver was carefully excised and rinsed immediately in ice-cold phosphate-buffered saline (PBS, pH 7.4) to remove residual blood. A weighed portion of liver tissue (~ 0.2–0.5 g) was homogenized in nine volumes (1:9, w/v) of ice-cold 0.1 M Tris-HCl buffer (pH 7.4) using a Teflon-glass homogenizer on ice to preserve enzymatic activity. The homogenate was centrifuged at 10,000 × g for 15 minutes at 4°C, and the resulting supernatant was collected for the enzymatic assay. GGT activity was determined spectrophotometrically according to the standard γ-glutamyl transfer reaction. The assay mixture contained 1.0 mM γ-glutamyl-p-nitroanilide as the γ-glutamyl donor substrate and 40 mM glycylglycine as the acceptor in 0.1 M Tris-HCl buffer (pH 8.2). The reaction was initiated by adding 0.1 mL of liver homogenate supernatant to 0.9 mL of substrate solution prewarmed at 37°C. The transfer of the γ-glutamyl group from γ-glutamyl-p-nitroanilide to glycylglycine releases p-nitroaniline, which produces a yellow color measurable at 405 nm using a spectrophotometer.Enzyme activity was expressed as units per milligram of protein (U/mg protein), where one unit (U) is defined as the amount of enzyme catalyzing the release of 1 µmol of p-nitroaniline per minute under assay conditions. Protein concentration of the homogenates was determined by the Brad ford method to normalize enzyme activity. Equipment and Chemicals Used for Determination of Hepatic GGT Activity in Rats For the determination of hepatic GGT activity in rats, equipment and chemicals produced or available in Iran were used, all meeting high precision and laboratory standards. Rats were anesthetized with an intraperitoneal injection of ketamine (80–100 mg/kg, 99% purity, produced by Exir Pharmaceutical Co., Iran) and xylazine (5–10 mg/kg, 98–99% purity, supplied by Darou Pakhsh, Iran), with an injection error of less than 5% and compliant with USP standards, sourced from veterinary pharmacies in Iran. The excised liver was rinsed in ice-cold PBS (pH 7.4, 99.5% purity, produced by Kimyagaran Emrooz, Iran). Approximately 0.2–0.5 g of liver tissue was homogenized in 0.1 M Tris-HCl buffer (pH 7.4, 99.5% purity) using a Teflon-glass homogenizer (Araco HS series, Iran, 500–2000 W, 20–30 kHz frequency, 99% precision), manufactured by knowledge-based companies Fanavaran Nano Meghyas, with a resolution of 0.1 µm and less than 2% error, preserving enzymatic activity. The homogenate was centrifuged at 10,000 × g for 15 minutes using a centrifuge (produced by FG or Parsian Tajhiz DaneshGostar, Iran, speed up to 15,000 × g, 4°C with ± 0.5°C accuracy, 10 rpm resolution, < 1% error) to obtain the supernatant. GGT activity was measured spectrophotometrically using a Pars Azmoon enzymatic kit (Iran, containing 1.0 mM γ-glutamyl-p-nitroanilide and 40 mM glycylglycine in Tris-HCl buffer pH 8.2, sensitivity 1 µmol/min, ± 5% precision) at 405 nm with a Nano Mabna Iranian spectrophotometer (0.1–1 nm resolution, ± 0.002 Abs accuracy, < 0.5% error). Chemicals like γ-glutamyl-p-nitroanilide and glycylglycine (98–99% purity, supplied by Kimyagaran Emrooz) had less than 1% error in the reaction. Protein concentration was determined using a Bradford assay kit from DNAbiotech (Iran, sensitivity 3 µg/ml, ± 2–5% precision, linear range 3–1000 µg/ml) at 595 nm. 2–4.Statistical methods and data analysis The statistical methods of mean, tables, and standard deviation were used. The normality of data distribution was checked by the Shapiro-Wilk test, the homogeneity of variance was checked by the Levine test, and the comparison of mean changes was checked by the two-way analysis of variance test. If the tests were significant, the Bonferroni post hoc test was used (P ≤ 0/05, SPSS 22 and Excel 2010 software). 3. Results Growth and Body Composition Indicators Rats in all groups showed progressive increases in body weight during the intervention period. However, the rate of weight gain was significantly lower in the HIIT + Livergol group compared to the control (p < 0.05). The Lee index was also significantly reduced in the trained and supplemented groups, indicating improved body composition and reduced adiposity. No significant differences were observed in daily food or water intake among groups, suggesting that the changes in body weight were primarily due to metabolic adaptations rather than reduced energy intake (Table 3 ). Table 3 Body weight, growth rate, and energy intake in different experimental groups Group Initial Body Weight (g) Final Body Weight (g) Average Growth Rate (g/week) Daily Food Intake (g/rat) Daily Energy Intake (kcal/rat) Control 246 ± 7 350 ± 20 10 ± 1 20 ± 0.5 60 ± 1.5 HIIT 250 ± 4 345 ± 15 9.5 ± 1 19 ± 0.4 57 ± 1.2 Livergol 246 ± 5 348 ± 10 9.8 ± 0.8 20 ± 0.5 59 ± 1.4 HIIT + Livergol 251 ± 2 340 ± 12 9 ± 0.8 19 ± 0.3 56 ± 1.0 Blood metabolic and biochemical indices (FBG, FINS, TC, TG, LDL-C, HDL-C, GGT, AST, ALT, and inflammatory markers) were measured and recorded for the groups (Table 4 ). Table 4 Metabolic and Biochemical Blood Parameters in Different Experimental Groups Group FBG (mg/dL) FINS (µIU/mL) TC (mg/dL) TG (mg/dL) LDL-C (mg/dL) HDL-C (mg/dL) GGT (U/L) AST (U/L) ALT (U/L) Control 145 ± 8 22 ± 2 180 ± 12 150 ± 10 110 ± 8 38 ± 4 40 ± 4 70 ± 5 50 ± 4 HIIT 130 ± 7 18 ± 2 160 ± 10 130 ± 8 90 ± 6 45 ± 4 32 ± 3 60 ± 4 42 ± 3 Livergol 135 ± 7 19 ± 2 165 ± 10 135 ± 9 95 ± 7 42 ± 3 35 ± 3 65 ± 4 45 ± 3 HIIT + Livergol 125 ± 6 16 ± 1.5 155 ± 9 120 ± 7 85 ± 6 48 ± 3 28 ± 2 55 ± 3 40 ± 2 To investigate the effect of the high-intensity exercise program, heart rate, the animals' time to fatigue and VO₂max were measured and recorded before and after the protocol period (Table 5 ). Table 5 Exercise performance in obese rats before and after 8 weeks Group Baseline VO₂max (mL/kg/min) VO₂max After 8 Weeks Baseline Time to Exhaustion (min) Time to Exhaustion After 8 Weeks (min) Heart Rate Week 0 (bpm) Heart Rate Week 8 (bpm) Control 37 ± 2 38 ± 2 12 ± 1.5 12 ± 1.5 360 ± 15 362 ± 15 HIIT 38 ± 2 49 ± 3 12 ± 1.5 19 ± 1.8 358 ± 14 370 ± 12 Livergol 37.5 ± 2 40 ± 2 12 ± 1.5 13 ± 1.3 359 ± 15 365 ± 13 HIIT + Livergol 38 ± 2 51 ± 3 12 ± 1.5 21 ± 1.5 358 ± 14 372 ± 12 The changes in PPARγ gene expression between the four control and experimental groups were calculated and recorded (Fig. 1 ). The results of the study showed that the increase in PPARγ gene expression was significant in the interaction groups of exercise and liver gel (ŋ=0.498, P = 0.018, F = 23.163), exercise (ŋ=0.338, P = 0.001, F = 13.170), and livergol intake (ŋ=0.298, P = 0.005, F = 8.271). The results of the Bonferroni test showed that the expression of PPARγ gene increased significantly in the groups of liver gel and exercise, liver gel and exercise compared to the control group. Also, the expression of PPARγ gene increased significantly in the groups of liver gel and exercise, liver gel and exercise compared to the control group. Finally, the interaction of exercise and liver gel caused a greater increase in the expression of the PPARγ gene compared to the other groups) Table 3 . ( Table 3 Results of analysis of variance for examining PPARγ gene expression and effect size Source of Variation df F-value p-value η² Mean ± SD (per group) Training × Livergol Interaction 1, 24 23.16 0.018 0.498 Control: 1.7 ± 0.1 Livergol: 2.85 ± 0.15 Exercise: 3.1 ± 0.15 Livergol + Exercise: 4.3 ± 0.2 Training 1, 24 13.17 0.001 0.338 Sedentary: 2.275 ± 0.175 Training: 3.7 ± 0.175 Livergol Administration 1, 24 8.27 0.005 0.298 Control: 1.7 ± 0.1 Livergol: 3.575 ± 0.175 Changes in GGT concentration between the four control and experimental groups were calculated and recorded (Fig. 2 ). Another finding of the study was the decrease in gammaglutamyl transferase concentration in the experimental groups. This decrease was significant in the interaction group of exercise and liver gel (ŋ=0.289, P = 0.001, F = 34.245), the exercise group (ŋ=0.265, P = 0.001, P = 29.543) and the liver gel intake (ŋ=0.210, P = 0.001, F = 12.659). The results of the Bonferroni test showed that the concentration of gammaglutamyl transferase decreased significantly in the liver gel and exercise groups, liver gel and exercise group, respectively, compared to the control group, and the interaction of exercise and liver gel caused a greater decrease in the concentration of gammaglutamyl transferase than in the other groups (Table 4 ). Table 4 Results of analysis of variance for GGT enzyme concentration and effect size (η²) Source of Variation df F (Value) p-value η² Mean ± SD (per group) Livorgol Administration 1, 24 34.245 0.001 0.289 Control: 44.03 ± 0.21 Livergol: 32.03 ± 0.2 Exercise: 28.04 ± 0.12 Livergol + Exercise: 23.45 ± 0.1 Training 1, 24 29.543 0.001 0.265 Training×Livorgol Interaction 1, 24 12.659 0.001 0.210 The Pearson correlation coefficient between PPARγ fold change and GGT level was approximately r = − 0.975. This value indicates a very strong, perfect, and inverse (negative) linear correlation between these two variables. It is statistically proven that as PPARγ fold change increases, GGT level decreases. 4. Discussion and Conclusion The results of the study showed that PPARγ was increased by intense interval training and livergol supplementation. PPARγ plays a crucial role in adipocyte differentiation, the expression of key enzymes involved in lipid metabolism, as well as hormone-sensitive lipase, and the differentiation of white and brown fat cells. In the present study, it can be said that intense interval training and livergol caused the possible activation of these mechanisms. In this regard, Fan et al. (2017) reported that the role of PPARγ in regulating metabolism and controlling insulin sensitivity and sugar catabolism could also be another factor in the increase of these proteins ( 12 ). Chan et al. (2024) also reported that controlling plasma lipid levels and inhibiting their increase increased PPARγ activity, and livergol supplementation probably improved this condition ( 13 ). Oxidative stress from exercise has acted as a stimulus for increasing PPARγ. Several exercise-sensitive signaling pathways may have intervened in this process. Exercise activates signals through PPARγ in skeletal myocytes, and exercise-related oxidative stress increases the level of PPARγ ligands. Also, increased aerobic respiration, which uses fat molecules as fuel and energy production in skeletal muscles, causes the release of fatty acids from adipose tissue, the advancement of PPARγ regulation by lipid consumption, and the clearance and reverse return of cholesterol in monocytes and macrophages( 14 ). Zhou et al. (2024) have considered previous exercise to be effective in increasing these proteins ( 15 ). Considering the effects of livergol on stress and inflammatory indices, it can also be said that the reduction of cytokines has been a suitable basis for strengthening the metabolic mechanism and increasing this protein ( 16 ). High-intensity interval training has caused a decrease in body fat mass and the development of this pathway ( 17 ). PPARs play a role in many physiological processes, such as inflammation and energy homeostasis. In general, PPARγ must be activated by ligands to stimulate the expression of its target genes. These agonists can be used as synthetic molecules and as drugs to treat hyperglycemia and insulin resistance or as natural physiological ligands, such as fatty acids and eicosanoids ( 18 ). Therefore, it seems that high-intensity interval training and livergol have played their role in increasing PPARγ well. The findings of the study are in contradiction with the results of Zhang rt al.(2025) and Nazari et al. (2023) ( 19 – 20 ). Of course, the duration of the training period, intensity, duration, volume, and force of physical activity play an important role in stimulating the gamma or alpha state of this protein. Nazari et al. did not use forced training and did not observe an increase. Zheng et al. (2025) investigated PPARα and focused on inflammatory and atherosclerosis indicators, while they had a different training protocol. Of course, the role of Livergol supplementation was also effective in obtaining the results of the present study, which was not present in their study ( 21 ). Pu et al. (2022) also obtained different results. They examined the PPAR delta index on vascular pathophysiology. However, they did not use a specific training protocol and supplementation ( 22 ). Another result of the present study was the reduction of the liver enzyme GGT as a result of intense interval training + Livergol supplementation. Interval training with short and intense segments caused fat burning and fat catabolism, resulting in a decrease in liver metabolic pressure and reduced liver enzyme secretion, which in turn led to less steatosis in mice. Also, the training protocol caused a decrease in the content of the hypoxia-inducible gene 2 (HIG2) and a decrease in the expression of liver fat genes and enzymes ( 23 ). Kamrul et al. (2024) studied the effect of silymarin on the levels of liver enzymes ALT and AST in patients with non-alcoholic fatty hepatitis and announced that silymarin can be effective in reducing the levels of liver enzymes in patients with non-alcoholic fatty hepatitis ( 24 ). However, this is in contrast to the results of the study by Razzak (2024), who considered some environmental interventions to be influential in changing the results. The proposed mechanism for the GGT-reducing effect of high-intensity interval training and liver oil on blood lipids and cholesterol seems to signaling pathway. Activation of PPARγ in the liver leads to increased fatty acid β-oxidation and decreased triglyceride synthesis. This decrease in triglycerides could also be due to decreased expression of hepatic apolipoprotein and lipoprotein lipase genes. In addition, activation of PPARα induces the expression of the above genes, which leads to increased plasma HDL-C in humans ( 25 ). PPARα agonists, like PPARγ, are effective in reducing GGT ( 26 ). Another possible mechanism for this reduction could be due to the interference of Livergol and the training protocol in energy metabolism pathways. One of the regulatory enzymes of metabolic pathways is AMPK, which is stimulated in response to cellular stress and an increase in the ratio of cellular ATP to AMP and regulates energy homeostasis through phosphorylation and inhibition of acetyl-CoA carboxylase (ACC). Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA, which acts as a barrier to fatty acid synthesis and inhibits fatty acid oxidation in muscle ( 27 ). In the study by Sharifi et al., plyometric training was used, and no supplements were used, so no changes in liver enzymes were observed. In this study, the Livergol supplement, which contains the flavonolignans silybin, silychristin, isosilybin, and silydianin with flavonoids, anti-inflammatory antioxidants, and immune system modulators, prevented the increase in steatosis with the help of interval training ( 7 ). The sex differences may play a critical role in the physiological and molecular responses to both exercise training and hepatoprotective agents such as Livergol. Female rodents, due to the influence of ovarian hormones, may exhibit distinct patterns of gene regulation, antioxidant activity, and enzymatic adaptations compared to males. Estrogen, for example, is known to exert protective effects on oxidative stress and mitochondrial function, which could potentially alter the expression of peroxisome proliferator-activated receptors (PPARs) and gamma-glutamyl transferase (GGT) activity ( 28 ). Therefore, while our findings provide valuable insights into the male response, extrapolation of these results to females must be done with caution. Mitochondrial function, oxidative phosphorylation, and bioenergetic capacity are key factors of cellular adaptation that can provide complementary evidence to support the transcriptional outcomes. High-intensity interval training (HIIT) and Livergol supplementation appear to have synergistic effects on hepatic metabolism through interconnected molecular pathways. HIIT increases cellular AMP/ATP ratio and leads to activation of AMP-activated protein kinase (AMPK), which subsequently increases PGC-1α activity and enhances PPAR-γ transcriptional activation( 29 ). Activated PPARγ, first phosphorylated by AMPK via HIIT and direct interaction with Livergol, translocates to the nucleus and binds to PPAR response elements to regulate the expression of target genes; this includes suppression of NF-κB via IKK inhibition and inhibition of the expression of proinflammatory cytokines such as TNF-α and IL-1β, which reduces chronic hepatic inflammation and GGT induction( 30 ). At the same time, PPARγ, by enhancing Nrf2 and activating HO-1, probably inhibits oxidative stress and improves glutathione metabolism, which directly lowers GGT levels. Interaction of PPARγ with PGC-1α increases fatty acid β-oxidation via CPT1 and ATGL and reduces hepatic steatosis, which limits secondary lipotoxicity and GGT-dependent inflammatory damage. In addition, activated PPAR-γ increases genes involved in lipid oxidation, glucose metabolism, and antioxidant defense, thereby improving metabolic homeostasis in hepatocytes. Increased AMPK activity also leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), which in turn reduces malonyl-CoA production( 31 ). Malonyl CoA reduction removes the inhibition of the CPT-1α enzyme and enhances the entry of fatty acids into mitochondria and, as a result, fat oxidation (via PPARα) and helps to clear fatty liver( 32 ). Livergol, with its strong antioxidant properties, probably neutralizes reactive oxygen species (ROS) and increases glutathione (GSH) reserves. GGT activity is a biochemical response to increased oxidative stress in the liver, and the reduction of oxidative stress by Livergol leads to a decrease in the regulation and activity of the GGT enzyme. In this regard, through the active component silymarin, it activates the Nrf2-ARE pathway and inhibits NF-κB signaling, reducing oxidative stress and inflammation. These effects further enhance PPAR-γ activity and stabilize liver cell function( 33 ). Limitations One of the limitations of this study was the exclusive use of male mice, so that the results of the study were not affected by changes in the physiological cycle of the female sex. Also, lipid examination, histology, and examination of liver fibrosis and oxidative capacity could provide insights into the mechanisms, but unfortunately, due to the financial burden of using biochemical markers in Iran, it was not possible to develop effective research. Due to laboratory facilities (ultrasound, tissue biopsy, and other related tests) and high costs in Iran, the weight of epididymal and kidney fat layers was not measured. Declarations Funding information This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution F.N. conceptualized and designed the study, while F.N. and A.K. performed the experiments and collected the data. Both F.N. and A.K. carried out the molecular analyses, as well as the statistical analyses, and interpreted the results. F.N. wrote the initial draft of the manuscript. All authors reviewed, edited, and approved the final version of the manuscript. Acknowledgement Data is provided within the manuscript or supplementary information files Data Availability Data is provided within the manuscript " References Sivell, C. Nonalcoholic Fatty Liver Disease: A Silent Epidemic. Gastroenterol Nurs. ; 42(5):428–434. (2019). 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2","display":"","copyAsset":false,"role":"figure","size":14557,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in GGT in the four study groups in terms of international units\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7831368/v1/4d27eec116ed79a9910eeab9.png"},{"id":95145707,"identity":"20e81230-fccb-400a-93b5-cabf7e170749","added_by":"auto","created_at":"2025-11-04 18:53:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31835,"visible":true,"origin":"","legend":"\u003cp\u003ePPARγ \u0026nbsp;uregulation correlates with decreased GGT levels following interventions\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7831368/v1/55ea14b1342691175fc3146e.png"},{"id":95225790,"identity":"e3458cd1-467f-4436-9877-40c0f60e3f5a","added_by":"auto","created_at":"2025-11-05 16:25:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":520586,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Introduction section.\u003c/p\u003e","description":"","filename":"UnnumberFigure.png","url":"https://assets-eu.researchsquare.com/files/rs-7831368/v1/264a0c44afdf0ff8452aa21b.png"},{"id":98814050,"identity":"8a555f4c-35bc-44ff-9965-36e0c147a8cc","added_by":"auto","created_at":"2025-12-22 16:10:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1712102,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7831368/v1/7e318ef4-7059-48dc-b07d-479a4768e5de.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Response of Peroxisome Proliferator-Activated Receptor Genes and Gamma- Glutamyl Transferase in Rats to High-Intensity Interval Training and Livergol","fulltext":[{"header":"Highlights","content":"\u003cp\u003e1. HIIT upregulated PPARα/γ expression, improving lipid metabolism.\u003c/p\u003e\u003cp\u003e2. HIIT enhanced hepatic function, aiding metabolic disorder control.\u003c/p\u003e\u003cp\u003e3. Livergol boosted antioxidant defense and lowered GGT activity.\u003c/p\u003e\u003cp\u003e4. HIIT\u0026thinsp;+\u0026thinsp;Livergol showed synergistic effects on liver genes and enzymes.\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eOverweight and obesity are major health concerns worldwide and have major epigenetic consequences, such as liver disorders. Fatty liver disease or steatosis is an example of liver cell damage that is influenced by genetic factors, lifestyle, diet, and physical activity status. Multidimensional approaches of nutritional control, weight loss, and exercise may be beneficial (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). An important training protocol is interval training, which consists of repeated short bouts of exercise with rest periods. In this training, physiological components are subjected to greater stress (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Exercise may cause physiological changes in liver fat content and expression of various genes. The use of medicinal plants is also recommended due to fewer side effects. Livergel may also be useful due to its silymarin content in strengthening the immune system, antioxidant effects, and enhancing liver cell regeneration. (2022) investigated the effect of silymarin supplementation on serum IL6 and CRP levels after a single aerobic exercise session in healthy men, which resulted in a reduction in inflammatory markers (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Treatment modalities for diseases and the efficacy of drugs effective in treating liver disorders, such as interferon and corticosteroids, although appropriate, have been inconsistent in many cases, and their side effects have been a barrier to prescription. Researchers have extensively studied herbal medicines as an alternative to chemical treatments. In a study by Sobolev et al. (2022), after 4 weeks of silymarin intake by patients, AST and ALT enzyme levels decreased. In animal studies, silymarin has also shown its protective effects against various liver toxins caused by hepatotoxic drugs. Studies have also been conducted on the transcription of peroxisome proliferator-activated receptor (PPARγ) and the molecular function of human factor (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The effect of activating PPARγ by GW0742, a specific agonist of this isoform, has also been investigated in mice. They differ in terms of chromosomal location, ligand affinity, target gene expression, and metabolic functions. Their biological functions have been observed in inflammation, obesity, and diabetes. Although exercise interventions have been shown to alter gene expression in some studies, no significant effects have been observed on lipid and aminotransferase profiles (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The present study aimed to investigate the efficacy of Livergol in improving liver function and to examine the effects of exercise on GGT and PPARγ in obese rats.\u003c/p\u003e\u003cp\u003eTherefore, the question now arises: Does livergol consumption and intense interval training affect the expression of the peroxisome proliferator-activated receptor gamma (PPARγ) gene and the gamma-glutamyl transpeptidase (GGT) enzyme in obese male rats?\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eResearch Methodology\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis research was fundamental and applied, and was conducted experimentally with a post-test design in four groups. The present study was conducted in the form of a two-group experimental design (experimental and control). The research population consisted of male Wistar rats. Accordingly, 50 male rats with an average weight of 246\u0026thinsp;\u0026plusmn;\u0026thinsp;15 grams were obtained from the Pasteur Laboratory Animal Breeding Center and transferred to the Animal Science Research Laboratory of the university, and were kept in the animal house environment for 1 week in order to adapt to the new conditions. The rats were cared for in transparent polycarbonate cages measuring 30\u0026times;15\u0026times;15cm, manufactured by Razi Rad Company, at a temperature of 22\u0026thinsp;\u0026plusmn;\u0026thinsp;3 degrees. All animal experiments were performed according to the ARRIVE guidelines and were in accordance with the Animal (Scientific Procedures) Act 1986 and related guidelines, the European Union Directive 2010/63 for the protection of animals used for scientific purposes, or the NIH (National Research Council) Guide for the Care and Use of Laboratory Animals. Institutional ethics approval number IR.IAU.VARAMIN.REC.1399.006 was obtained from the Ethics Committee of the Faculty of Medicine, Islamic Azad University, Varamin Pishva Branch.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e2\u0026thinsp;\u0026minus;\u0026thinsp;1. Experimental Design and Intervention Protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo induce weight gain and establish a high-calorie dietary model in rats, we employed a hypercaloric diet enriched with fat and simple carbohydrates. The diet was formulated to provide approximately 4.5\u0026ndash;5.2 kcal/g, which is considerably higher than the ~\u0026thinsp;3 kcal/g of standard chow. Specifically, the macronutrient composition consisted of 40\u0026ndash;45% of total energy from fat (derived from sources such as soybean oil, coconut oil, or lard), 35\u0026ndash;40% from carbohydrates (a mixture of cornstarch and sucrose), and 15\u0026ndash;20% from protein (primarily casein or soy protein). In addition, the diet was supplemented with approximately 5% cellulose as a source of fiber, along with standard mineral and vitamin mixtures according to the AIN-93 formulation. An example formulation, per 100 g of diet, included: 20 g of casein, 25 g of fat, 30 g of cornstarch, 15 g of sucrose, 5 g of cellulose, 2 g of vitamin mixture, and 3 g of mineral mixture(\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e). This hypercaloric regimen has been shown to significantly promote body weight gain, with male rats typically increasing from approximately 246g to 330-350g within 6\u0026ndash;10 weeks of feeding. All animals were weighed once or twice per week throughout the study period using a digital precision balance, and weekly growth curves were plotted for each group. Daily food and water intake were recorded to calculate average energy intake per cage. At the end of the experimental protocol, the Lee index was calculated as an indicator of adiposity and metabolic status using the formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" style=\"width: 282px; height: 58.3978px;\" width=\"282\" height=\"58.3978\"\u003e\u003c/p\u003e\n\u003cp\u003eThis diet induced general weight gain and metabolic alterations (increased triglycerides, hepatic steatosis, and insulin resistance).Resting heart rate was measured using a tail-cuff plethysmography system. Prior to recording, the mice were placed in a quiet environment for several minutes to minimize stress and obtain accurate measurements. The behavioral status of the mice was monitored daily and assessed based on parameters such as locomotor activity, self-grooming, responsiveness to environmental stimuli, and signs of stress or lethargy. Each animal was evaluated using a six-point scale, where 6 indicated a highly active and responsive state, and 1 represented lethargy or severe stress.\u003c/p\u003e\n\u003cp\u003eWhen the weight of the mice increased to 350\u0026thinsp;\u0026plusmn;\u0026thinsp;20 g, they were divided into four groups of ten, including the exercise group, the livergol group, the exercise\u0026thinsp;+\u0026thinsp;livergol group, and the control group, and familiarization with the laboratory environment and the main exercise protocol began. Thus, the exercise group was exposed to intense interval training for 8 weeks. The supplement group received livergol supplements for 8 weeks. In addition to the supplements, the exercise group underwent intense interval training for 8 weeks, which was accompanied by the consumption of livergol supplements.\u003c/p\u003e\n\u003cp\u003eLivergol tablets were obtained from Goldaru Herbal Pharmaceutical Company (Isfahan, Iran) under a valid health license issued by the General Directorate of Food and Drug Supervision, Ministry of Health (Batch No. LG-2401, Certificate of Analysis No.COA-2024-117). Each Livergol tablet contains 140 mg of standardized milk thistle (Silybum marianum) extract, equivalent to approximately 70\u0026ndash;80% silymarin, of which silybin is the major active flavonolignan component(\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFor experimental use, tablets were finely powdered and freshly prepared each day by suspending the powder in a 0.5% carboxymethyl cellulose solution as a vehicle. The compound was dissolved at room temperature to achieve the desired concentration, ensuring complete solubility and avoiding precipitation. Freshly prepared solutions were used for each administration.\u003c/p\u003e\n\u003cp\u003eLivergol was administered orally by gavage at a dose of 300 mg/kg body weight, once daily between 8:00 and 9:00 am. The selected dose (300 mg/kg) was based on previous animal studies demonstrating hepatoprotective and antioxidant effects of milk thistle extract without inducing toxicity in rats. After gavage, animals were observed for 3\u0026ndash;5 minutes to ensure full ingestion, and only those that had completely swallowed the solution were returned to their home cages. This procedure was performed consistently to guarantee accurate dosing and reliable experimental outcomes (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe control and exercise\u0026thinsp;+\u0026thinsp;placebo groups received maltodextrin in the same form so that all four groups were equally exposed to the physiological effects of gavage. A conveyor belt model A1400Y10, Pishro Andisheh Sanat Company, made in Iran, was used in this study. The conveyor belt slope was considered zero in all stages (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e). In the present study, only male Wistar rats were studied to minimize the potential confounding effects of the physiological cycle in females and to avoid the study being affected by fluctuations in estrogen and progesterone levels. Changes in sex hormones can significantly affect metabolic, enzymatic, and gene expression responses. By limiting the study to males, we aimed to reduce biological variability and increase the internal validity of the findings.The control group did not take any supplements and did intense interval training (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eHigh-intensity interval training program (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWeek\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdd days (Moderate intensity)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEven days (High intensity)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRest between bouts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIncline (\u0026deg;)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSessions/week\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWarm-up / Cool-down\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eProgression\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 \u0026times; 3 min at 40 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;5 \u0026times; 30 s at 54 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 s active rest at 16 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 min at 16 m/min (before \u0026amp; after)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStart phase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 \u0026times; 3 min at 40 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u0026ndash;7 \u0026times; 30 s at 54 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 s active rest at 16 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 min at 16 m/min (before \u0026amp; after)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradual increase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u0026ndash;5 \u0026times; 3 min at 40 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u0026ndash;9 \u0026times; 30 s at 54 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 s active rest at 16 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 min at 16 m/min (before \u0026amp; after)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncreased load\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026ndash;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u0026ndash;6 \u0026times; 3 min at 40 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u0026ndash;11 \u0026times; 30 s at 54 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 s active rest at 16 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 min at 16 m/min (before \u0026amp; after)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNear-maximum load\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 \u0026times; 3 min at 40 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 \u0026times; 30 s at 54 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 s active rest at 16 m/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 min at 16 m/min (before \u0026amp; after)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeak phase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTo eliminate the effects of the training protocol and uncontrollable variables that may have occurred during the exercise, the day after the last training session (24 hours), they were anesthetized by ethical principles and intraperitoneal injection of a combination of ketamine (70 mg/kg) and xylazine (3\u0026ndash;5 mg/kg). After dissecting the animals, adipose tissue was removed from the subcutaneous epidermal fat layer of the mice and washed in physiological saline. It was then immediately frozen with liquid nitrogen at a temperature of -80 degrees Celsius and stored for later examination.\u003c/p\u003e\n\u003cp\u003eAfter the final training session, all animals were euthanized according to ethical standards to minimize pain and distress. Anesthesia was induced by intraperitoneal injection of ketamine (90 mg/kg) and xylazine (10 mg/kg), followed by an overdose of sodium pentobarbital (200 mg/kg, i.p.) for euthanasia. All procedures were conducted in accordance with the institutional guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Ethics Committee (Ethics code: IR.IAU.VARAMIN.REC.1399.006).\u003c/p\u003e\n\u003ch3\u003e2\u0026ndash;2.PPAR\u0026gamma; gene expression study using the RT-PCR technique\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e2\u0026ndash;2.PPAR\u0026gamma; gene expression study using the RT-PCR technique\u003c/div\u003e\n\u003cp\u003eThe expression of Peroxisome Proliferator-Activated Receptor Gamma (PPAR\u0026gamma;) was assessed using reverse transcription quantitative PCR (RT-qPCR). Specific primers for the target gene (PPAR\u0026gamma;) and the reference gene (\u0026beta;-actin) were designed using the NCBI database and Primer-BLAST (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Primer design criteria included specificity, melting temperature (Tm\u0026thinsp;~\u0026thinsp;60\u0026deg;C), absence of significant secondary structures, and amplicon size between 100\u0026ndash;200 bp.\u003c/p\u003e\n\u003cp\u003eRNA extraction and cDNA synthesis: Total RNA was isolated from tissues using the Qiagen RNA extraction kit (Qiagen, Germany) following the manufacturer\u0026rsquo;s protocol. RNA quantity and purity were assessed using a Nanodrop spectrophotometer (Thermo Scientific, USA). Only samples with an A260/A280 ratio between 1.8\u0026ndash;2.0 were used for cDNA synthesis. Reverse transcription was performed with a Qiagen cDNA synthesis kit according to the manufacturer\u0026rsquo;s instructions.\u003c/p\u003e\n\u003cp\u003eqPCR amplification\u003c/p\u003e\n\u003cp\u003eqPCR reactions were performed in triplicate using SYBR Green dye on a Real-Time PCR system (Applied Biosystems, USA). Thermal cycling conditions were: initial denaturation at 95\u0026deg;C for 5 min, followed by 35 cycles of 95\u0026deg;C for 30 s, 60\u0026deg;C for 30 s, and 72\u0026deg;C for 30 s, with a final extension at 72\u0026deg;C for 5 min.\u003c/p\u003e\n\u003cp\u003eValidation and quality control:\u003c/p\u003e\n\u003cp\u003eAmplification efficiency for each primer pair was determined by generating standard curves from a 5-fold serial dilution of cDNA; efficiencies ranged between 90\u0026ndash;105%.\u003c/p\u003e\n\u003cp\u003eMelt curve analysis was performed at the end of each run to confirm the specificity of amplification, ensuring a single peak per primer pair.\u003c/p\u003e\n\u003cp\u003eSelected PCR products were further validated by agarose gel electrophoresis to confirm the expected product size.\u003c/p\u003e\n\u003cp\u003eThe stability of \u0026beta;-actin expression was confirmed across all experimental groups; additionally, a second housekeeping gene (GAPDH) was assessed to ensure normalization reliability.\u003c/p\u003e\n\u003cp\u003eData analysis\u003c/p\u003e\n\u003cp\u003eRelative gene expression was calculated using the \u0026Delta;\u0026Delta;Ct method. First, the difference in Ct values between the target and reference gene (\u0026Delta;Ct) was determined for each sample. Then, the \u0026Delta;Ct of the intervention groups was compared with the control group to obtain \u0026Delta;\u0026Delta;Ct. Fold change in gene expression was calculated as 2^-\u0026Delta;\u0026Delta;Ct and reported accordingly(\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePrimer information for examining PPAR\u0026gamma; gene expression.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTarget gene\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eProduct size (bp)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTm (\u0026deg;C)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePrimer sequence (5\u0026prime;\u0026rarr;3\u0026prime;)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirection\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSource / Reference\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ePPAR\u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAGGCCGAGAAGGAGAAGCTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForward\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesigned using NCBI Primer-BLAST\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTGGCCACCTCTTTGCTCTA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesigned using NCBI Primer-BLAST\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026beta;-actin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAGAGGGAAATCGTGCGTGAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForward\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesigned using NCBI Primer-BLAST\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAATAGTGATGACCTGGCCGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesigned using NCBI Primer-BLAST\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGAPDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAGGTCGGTGTGAACGGATTTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForward\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimerBank ID: 6679937a1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGAPDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTGTAGACCATGTAGTTGAGGTCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimerBank ID: 6679937a1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003e2\u0026ndash;3.Investigation of GGT Biochemical Index\u003c/h3\u003e\n\u003cp\u003eRats were anesthetized with an intraperitoneal injection of ketamine (80\u0026ndash;100 mg/kg body weight) and xylazine (5\u0026ndash;10 mg/kg body weight). Following confirmation of deep anesthesia, the abdominal cavity was opened, and the liver was carefully excised and rinsed immediately in ice-cold phosphate-buffered saline (PBS, pH 7.4) to remove residual blood. A weighed portion of liver tissue (~\u0026thinsp;0.2\u0026ndash;0.5 g) was homogenized in nine volumes (1:9, w/v) of ice-cold 0.1 M Tris-HCl buffer (pH 7.4) using a Teflon-glass homogenizer on ice to preserve enzymatic activity. The homogenate was centrifuged at 10,000 \u0026times; g for 15 minutes at 4\u0026deg;C, and the resulting supernatant was collected for the enzymatic assay.\u003c/p\u003e\n\u003cp\u003eGGT activity was determined spectrophotometrically according to the standard \u0026gamma;-glutamyl transfer reaction. The assay mixture contained 1.0 mM \u0026gamma;-glutamyl-p-nitroanilide as the \u0026gamma;-glutamyl donor substrate and 40 mM glycylglycine as the acceptor in 0.1 M Tris-HCl buffer (pH 8.2). The reaction was initiated by adding 0.1 mL of liver homogenate supernatant to 0.9 mL of substrate solution prewarmed at 37\u0026deg;C. The transfer of the \u0026gamma;-glutamyl group from \u0026gamma;-glutamyl-p-nitroanilide to glycylglycine releases p-nitroaniline, which produces a yellow color measurable at 405 nm using a spectrophotometer.Enzyme activity was expressed as units per milligram of protein (U/mg protein), where one unit (U) is defined as the amount of enzyme catalyzing the release of 1 \u0026micro;mol of p-nitroaniline per minute under assay conditions. Protein concentration of the homogenates was determined by the Brad ford method to normalize enzyme activity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEquipment and Chemicals Used for Determination of Hepatic GGT Activity in Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the determination of hepatic GGT activity in rats, equipment and chemicals produced or available in Iran were used, all meeting high precision and laboratory standards. Rats were anesthetized with an intraperitoneal injection of ketamine (80\u0026ndash;100 mg/kg, 99% purity, produced by Exir Pharmaceutical Co., Iran) and xylazine (5\u0026ndash;10 mg/kg, 98\u0026ndash;99% purity, supplied by Darou Pakhsh, Iran), with an injection error of less than 5% and compliant with USP standards, sourced from veterinary pharmacies in Iran. The excised liver was rinsed in ice-cold PBS (pH 7.4, 99.5% purity, produced by Kimyagaran Emrooz, Iran). Approximately 0.2\u0026ndash;0.5 g of liver tissue was homogenized in 0.1 M Tris-HCl buffer (pH 7.4, 99.5% purity) using a Teflon-glass homogenizer (Araco HS series, Iran, 500\u0026ndash;2000 W, 20\u0026ndash;30 kHz frequency, 99% precision), manufactured by knowledge-based companies Fanavaran Nano Meghyas, with a resolution of 0.1 \u0026micro;m and less than 2% error, preserving enzymatic activity. The homogenate was centrifuged at 10,000 \u0026times; g for 15 minutes using a centrifuge (produced by FG or Parsian Tajhiz DaneshGostar, Iran, speed up to 15,000 \u0026times; g, 4\u0026deg;C with \u0026plusmn;\u0026thinsp;0.5\u0026deg;C accuracy, 10 rpm resolution, \u0026lt;\u0026thinsp;1% error) to obtain the supernatant. GGT activity was measured spectrophotometrically using a Pars Azmoon enzymatic kit (Iran, containing 1.0 mM \u0026gamma;-glutamyl-p-nitroanilide and 40 mM glycylglycine in Tris-HCl buffer pH 8.2, sensitivity 1 \u0026micro;mol/min, \u0026plusmn;\u0026thinsp;5% precision) at 405 nm with a Nano Mabna Iranian spectrophotometer (0.1\u0026ndash;1 nm resolution, \u0026plusmn;\u0026thinsp;0.002 Abs accuracy, \u0026lt;\u0026thinsp;0.5% error). Chemicals like \u0026gamma;-glutamyl-p-nitroanilide and glycylglycine (98\u0026ndash;99% purity, supplied by Kimyagaran Emrooz) had less than 1% error in the reaction. Protein concentration was determined using a Bradford assay kit from DNAbiotech (Iran, sensitivity 3 \u0026micro;g/ml, \u0026plusmn;\u0026thinsp;2\u0026ndash;5% precision, linear range 3\u0026ndash;1000 \u0026micro;g/ml) at 595 nm.\u003c/p\u003e\n\u003ch3\u003e2\u0026ndash;4.Statistical methods and data analysis\u003c/h3\u003e\n\u003cp\u003eThe statistical methods of mean, tables, and standard deviation were used. The normality of data distribution was checked by the Shapiro-Wilk test, the homogeneity of variance was checked by the Levine test, and the comparison of mean changes was checked by the two-way analysis of variance test. If the tests were significant, the Bonferroni post hoc test was used (P\u0026thinsp;\u0026le;\u0026thinsp;0/05, SPSS 22 and Excel 2010 software).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eGrowth and Body Composition Indicators\u003c/p\u003e\u003cp\u003eRats in all groups showed progressive increases in body weight during the intervention period. However, the rate of weight gain was significantly lower in the HIIT\u0026thinsp;+\u0026thinsp;Livergol group compared to the control (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The Lee index was also significantly reduced in the trained and supplemented groups, indicating improved body composition and reduced adiposity. No significant differences were observed in daily food or water intake among groups, suggesting that the changes in body weight were primarily due to metabolic adaptations rather than reduced energy intake (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBody weight, growth rate, and energy intake in different experimental groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInitial Body Weight (g)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFinal Body Weight (g)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAverage Growth Rate (g/week)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDaily Food Intake (g/rat)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDaily Energy Intake (kcal/rat)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e246\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e350\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e250\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e345\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLivergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e246\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e348\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u0026thinsp;+\u0026thinsp;Livergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e251\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e340\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBlood metabolic and biochemical indices (FBG, FINS, TC, TG, LDL-C, HDL-C, GGT, AST, ALT, and inflammatory markers) were measured and recorded for the groups (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMetabolic and Biochemical Blood Parameters in Different Experimental Groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFBG (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFINS (\u0026micro;IU/mL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTC (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTG (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLDL-C (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHDL-C (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGGT (U/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAST (U/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e145\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e180\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e150\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e110\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c10\"\u003e\u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e130\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e160\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e130\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e90\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e32\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e60\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c10\"\u003e\u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLivergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e135\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e165\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e135\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e35\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c10\"\u003e\u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u0026thinsp;+\u0026thinsp;Livergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e125\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e155\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e120\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e85\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e28\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e55\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c10\"\u003e\u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTo investigate the effect of the high-intensity exercise program, heart rate, the animals' time to fatigue and VO₂max were measured and recorded before and after the protocol period (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eExercise performance in obese rats before and after 8 weeks\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline VO₂max (mL/kg/min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVO₂max After 8 Weeks\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBaseline Time to Exhaustion (min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTime to Exhaustion After 8 Weeks (min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHeart Rate Week 0 (bpm)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHeart Rate Week 8 (bpm)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e360\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e362\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e358\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e370\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLivergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e37.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e359\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e365\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIIT\u0026thinsp;+\u0026thinsp;Livergol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e358\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e372\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe changes in PPARγ gene expression between the four control and experimental groups were calculated and recorded (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe results of the study showed that the increase in PPARγ gene expression was significant in the interaction groups of exercise and liver gel (ŋ=0.498, P\u0026thinsp;=\u0026thinsp;0.018, F\u0026thinsp;=\u0026thinsp;23.163), exercise (ŋ=0.338, P\u0026thinsp;=\u0026thinsp;0.001, F\u0026thinsp;=\u0026thinsp;13.170), and livergol intake (ŋ=0.298, P\u0026thinsp;=\u0026thinsp;0.005, F\u0026thinsp;=\u0026thinsp;8.271). The results of the Bonferroni test showed that the expression of PPARγ gene increased significantly in the groups of liver gel and exercise, liver gel and exercise compared to the control group. Also, the expression of PPARγ gene increased significantly in the groups of liver gel and exercise, liver gel and exercise compared to the control group. Finally, the interaction of exercise and liver gel caused a greater increase in the expression of the PPARγ gene compared to the other groups) Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e3\u003c/span\u003e. (\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eResults of analysis of variance for examining PPARγ gene expression and effect size\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSource of Variation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003edf\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eη\u0026sup2;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (per group)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraining \u0026times; Livergol Interaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.498\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eControl: 1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\u003cp\u003eLivergol: 2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003cp\u003eExercise: 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003cp\u003eLivergol\u0026thinsp;+\u0026thinsp;Exercise: 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraining\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSedentary: 2.275\u0026thinsp;\u0026plusmn;\u0026thinsp;0.175\u003c/p\u003e\u003cp\u003eTraining: 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.175\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLivergol Administration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.298\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eControl: 1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\u003cp\u003eLivergol: 3.575\u0026thinsp;\u0026plusmn;\u0026thinsp;0.175\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eChanges in GGT concentration between the four control and experimental groups were calculated and recorded (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAnother finding of the study was the decrease in gammaglutamyl transferase concentration in the experimental groups. This decrease was significant in the interaction group of exercise and liver gel (ŋ=0.289, P\u0026thinsp;=\u0026thinsp;0.001, F\u0026thinsp;=\u0026thinsp;34.245), the exercise group (ŋ=0.265, P\u0026thinsp;=\u0026thinsp;0.001, P\u0026thinsp;=\u0026thinsp;29.543) and the liver gel intake (ŋ=0.210, P\u0026thinsp;=\u0026thinsp;0.001, F\u0026thinsp;=\u0026thinsp;12.659). The results of the Bonferroni test showed that the concentration of gammaglutamyl transferase decreased significantly in the liver gel and exercise groups, liver gel and exercise group, respectively, compared to the control group, and the interaction of exercise and liver gel caused a greater decrease in the concentration of gammaglutamyl transferase than in the other groups (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eResults of analysis of variance for GGT enzyme concentration and effect size (η\u0026sup2;)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSource of Variation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003edf\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF (Value)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eη\u0026sup2;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (per group)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLivorgol Administration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34.245\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.289\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eControl: 44.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e\u003cp\u003eLivergol: 32.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\u003cp\u003eExercise: 28.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\u003cp\u003eLivergol\u0026thinsp;+\u0026thinsp;Exercise: 23.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraining\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.543\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.265\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraining\u0026times;Livorgol Interaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12.659\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.210\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe Pearson correlation coefficient between PPARγ fold change and GGT level was approximately r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.975. This value indicates a very strong, perfect, and inverse (negative) linear correlation between these two variables. It is statistically proven that as PPARγ fold change increases, GGT level decreases.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"4. Discussion and Conclusion","content":"\u003cp\u003eThe results of the study showed that PPARγ was increased by intense interval training and livergol supplementation. PPARγ plays a crucial role in adipocyte differentiation, the expression of key enzymes involved in lipid metabolism, as well as hormone-sensitive lipase, and the differentiation of white and brown fat cells. In the present study, it can be said that intense interval training and livergol caused the possible activation of these mechanisms. In this regard, Fan et al. (2017) reported that the role of PPARγ in regulating metabolism and controlling insulin sensitivity and sugar catabolism could also be another factor in the increase of these proteins (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Chan et al. (2024) also reported that controlling plasma lipid levels and inhibiting their increase increased PPARγ activity, and livergol supplementation probably improved this condition (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Oxidative stress from exercise has acted as a stimulus for increasing PPARγ. Several exercise-sensitive signaling pathways may have intervened in this process. Exercise activates signals through PPARγ in skeletal myocytes, and exercise-related oxidative stress increases the level of PPARγ ligands. Also, increased aerobic respiration, which uses fat molecules as fuel and energy production in skeletal muscles, causes the release of fatty acids from adipose tissue, the advancement of PPARγ regulation by lipid consumption, and the clearance and reverse return of cholesterol in monocytes and macrophages(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Zhou et al. (2024) have considered previous exercise to be effective in increasing these proteins (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Considering the effects of livergol on stress and inflammatory indices, it can also be said that the reduction of cytokines has been a suitable basis for strengthening the metabolic mechanism and increasing this protein (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). High-intensity interval training has caused a decrease in body fat mass and the development of this pathway (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). PPARs play a role in many physiological processes, such as inflammation and energy homeostasis. In general, PPARγ must be activated by ligands to stimulate the expression of its target genes. These agonists can be used as synthetic molecules and as drugs to treat hyperglycemia and insulin resistance or as natural physiological ligands, such as fatty acids and eicosanoids (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Therefore, it seems that high-intensity interval training and livergol have played their role in increasing PPARγ well. The findings of the study are in contradiction with the results of Zhang rt al.(2025) and Nazari et al. (2023) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Of course, the duration of the training period, intensity, duration, volume, and force of physical activity play an important role in stimulating the gamma or alpha state of this protein. Nazari et al. did not use forced training and did not observe an increase. Zheng et al. (2025) investigated PPARα and focused on inflammatory and atherosclerosis indicators, while they had a different training protocol. Of course, the role of Livergol supplementation was also effective in obtaining the results of the present study, which was not present in their study (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Pu et al. (2022) also obtained different results. They examined the PPAR delta index on vascular pathophysiology. However, they did not use a specific training protocol and supplementation (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnother result of the present study was the reduction of the liver enzyme GGT as a result of intense interval training\u0026thinsp;+\u0026thinsp;Livergol supplementation. Interval training with short and intense segments caused fat burning and fat catabolism, resulting in a decrease in liver metabolic pressure and reduced liver enzyme secretion, which in turn led to less steatosis in mice. Also, the training protocol caused a decrease in the content of the hypoxia-inducible gene 2 (HIG2) and a decrease in the expression of liver fat genes and enzymes (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Kamrul et al. (2024) studied the effect of silymarin on the levels of liver enzymes ALT and AST in patients with non-alcoholic fatty hepatitis and announced that silymarin can be effective in reducing the levels of liver enzymes in patients with non-alcoholic fatty hepatitis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, this is in contrast to the results of the study by Razzak (2024), who considered some environmental interventions to be influential in changing the results. The proposed mechanism for the GGT-reducing effect of high-intensity interval training and liver oil on blood lipids and cholesterol seems to signaling pathway. Activation of PPARγ in the liver leads to increased fatty acid β-oxidation and decreased triglyceride synthesis. This decrease in triglycerides could also be due to decreased expression of hepatic apolipoprotein and lipoprotein lipase genes. In addition, activation of PPARα induces the expression of the above genes, which leads to increased plasma HDL-C in humans (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). PPARα agonists, like PPARγ, are effective in reducing GGT (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnother possible mechanism for this reduction could be due to the interference of Livergol and the training protocol in energy metabolism pathways. One of the regulatory enzymes of metabolic pathways is AMPK, which is stimulated in response to cellular stress and an increase in the ratio of cellular ATP to AMP and regulates energy homeostasis through phosphorylation and inhibition of acetyl-CoA carboxylase (ACC). Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA, which acts as a barrier to fatty acid synthesis and inhibits fatty acid oxidation in muscle (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In the study by Sharifi et al., plyometric training was used, and no supplements were used, so no changes in liver enzymes were observed.\u003c/p\u003e\u003cp\u003eIn this study, the Livergol supplement, which contains the flavonolignans silybin, silychristin, isosilybin, and silydianin with flavonoids, anti-inflammatory antioxidants, and immune system modulators, prevented the increase in steatosis with the help of interval training (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe sex differences may play a critical role in the physiological and molecular responses to both exercise training and hepatoprotective agents such as Livergol. Female rodents, due to the influence of ovarian hormones, may exhibit distinct patterns of gene regulation, antioxidant activity, and enzymatic adaptations compared to males. Estrogen, for example, is known to exert protective effects on oxidative stress and mitochondrial function, which could potentially alter the expression of peroxisome proliferator-activated receptors (PPARs) and gamma-glutamyl transferase (GGT) activity (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Therefore, while our findings provide valuable insights into the male response, extrapolation of these results to females must be done with caution. Mitochondrial function, oxidative phosphorylation, and bioenergetic capacity are key factors of cellular adaptation that can provide complementary evidence to support the transcriptional outcomes.\u003c/p\u003e\u003cp\u003eHigh-intensity interval training (HIIT) and Livergol supplementation appear to have synergistic effects on hepatic metabolism through interconnected molecular pathways. HIIT increases cellular AMP/ATP ratio and leads to activation of AMP-activated protein kinase (AMPK), which subsequently increases PGC-1α activity and enhances PPAR-γ transcriptional activation(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Activated PPARγ, first phosphorylated by AMPK via HIIT and direct interaction with Livergol, translocates to the nucleus and binds to PPAR response elements to regulate the expression of target genes; this includes suppression of NF-κB via IKK inhibition and inhibition of the expression of proinflammatory cytokines such as TNF-α and IL-1β, which reduces chronic hepatic inflammation and GGT induction(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). At the same time, PPARγ, by enhancing Nrf2 and activating HO-1, probably inhibits oxidative stress and improves glutathione metabolism, which directly lowers GGT levels. Interaction of PPARγ with PGC-1α increases fatty acid β-oxidation via CPT1 and ATGL and reduces hepatic steatosis, which limits secondary lipotoxicity and GGT-dependent inflammatory damage. In addition, activated PPAR-γ increases genes involved in lipid oxidation, glucose metabolism, and antioxidant defense, thereby improving metabolic homeostasis in hepatocytes. Increased AMPK activity also leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), which in turn reduces malonyl-CoA production(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Malonyl CoA reduction removes the inhibition of the CPT-1α enzyme and enhances the entry of fatty acids into mitochondria and, as a result, fat oxidation (via PPARα) and helps to clear fatty liver(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLivergol, with its strong antioxidant properties, probably neutralizes reactive oxygen species (ROS) and increases glutathione (GSH) reserves. GGT activity is a biochemical response to increased oxidative stress in the liver, and the reduction of oxidative stress by Livergol leads to a decrease in the regulation and activity of the GGT enzyme. In this regard, through the active component silymarin, it activates the Nrf2-ARE pathway and inhibits NF-κB signaling, reducing oxidative stress and inflammation. These effects further enhance PPAR-γ activity and stabilize liver cell function(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOne of the limitations of this study was the exclusive use of male mice, so that the results of the study were not affected by changes in the physiological cycle of the female sex. Also, lipid examination, histology, and examination of liver fibrosis and oxidative capacity could provide insights into the mechanisms, but unfortunately, due to the financial burden of using biochemical markers in Iran, it was not possible to develop effective research. Due to laboratory facilities (ultrasound, tissue biopsy, and other related tests) and high costs in Iran, the weight of epididymal and kidney fat layers was not measured.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding information\u003c/h2\u003e\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF.N. conceptualized and designed the study, while F.N. and A.K. performed the experiments and collected the data. Both F.N. and A.K. carried out the molecular analyses, as well as the statistical analyses, and interpreted the results. F.N. wrote the initial draft of the manuscript. All authors reviewed, edited, and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript or supplementary information files\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript \"\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSivell, C. Nonalcoholic Fatty Liver Disease: A Silent Epidemic. Gastroenterol Nurs. ; 42(5):428\u0026ndash;434. (2019). Sep/Oct \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/SGA.0000000000000443\u003c/span\u003e\u003cspan address=\"10.1097/SGA.0000000000000443\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31574071.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKent, J. A. \u0026amp; Hayes, K. L. 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Mitochondrial CPT1A: Insights into structure, function, and basis for drug development. \u003cem\u003eFront. Pharmacol.\u003c/em\u003e 1160440. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fphar\u003c/span\u003e\u003cspan address=\"10.3389/fphar\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023). ,2023;14,1160440.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDelli Bovi, A. P. et al. Oxidative Stress in Non-alcoholic Fatty Liver Disease. \u003cem\u003eUpdated Mini Rev. Front. Med.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 595371. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fmed.2021.595371\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2021.595371\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Livergol, high-intensity interval training, Proliferator-Activated Receptor, Gamma-Glutamyl Transferase, Genes ","lastPublishedDoi":"10.21203/rs.3.rs-7831368/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7831368/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Obesity is a major health problem and has many clinical consequences on the body's organs. Genetic factors, lifestyle, diet, and physical activity can play an effective role in weight control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This study aimed to investigate the effect of a period of intense interval training and Livergol supplementation on PPARγ and GGT in obese rats.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e: The statistical sample of the present study consisted of 40 male Wistar rats, which, after obesity was induced, were divided into four groups of ten: a control group, an exercise group (intensive interval training), a supplement group (Livergol supplementation), and an interval exercise and Livergol supplementation group. After completing the 8-week exercise and supplementation protocol, samples were collected from the adipose tissue and heart of the rats in the fasting state and on the day after the last exercise session, and then transferred to the reference laboratory. For statistical analysis, mean, standard deviation, Shapiro-Wilk, Levine tests, and two-way analysis of variance were used. If the results were significant, the Bonferroni test was used to determine the changes (P≤0/05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The expression level ofthe PPARγ gene was lower in the control group and the Livergol supplement group, but it increased in the exercise group and the exercise + Livergol group. The activity level of GGT enzymes was higher in the control group than in the Livergol, exercise, and exercise + Livergol supplement groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e \u0026nbsp;and \u003cstrong\u003eConclusion:\u003c/strong\u003eAccording to the study's results, it can be concluded that consuming Livergol and engaging in intense interval exercise has been effective in reducing liver damage and enzyme disorders by influencing sugar and fat metabolism and increasing the expression of the PPARγ gene. Additionally, engaging in periodic and intense exercise activities, combined with the consumption of Livergol, may have a positive effect on the regulation of the GGT enzyme.\u003c/p\u003e","manuscriptTitle":"Response of Peroxisome Proliferator-Activated Receptor Genes and Gamma- Glutamyl Transferase in Rats to High-Intensity Interval Training and Livergol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-04 18:53:29","doi":"10.21203/rs.3.rs-7831368/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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