Comparative Study on the Effects of High-Fat Diet and Capsicum Diet on the Digestive Organs of Guinea Pigs

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Experimental Methods: A total of 24 male Hartley guinea pigs were apportioned randomly and equally into three groups: the control group (n=8), the high-fat diet group (n=8), and the capsicum diet group (n=8). After 12 weeks of modeling, samples were collected from the abdominal aorta serum, liver, gallbladder, stomach, and colon. Biochemical analysis for the serum total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein cholesterol. Inflammatory markers in the serum, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining (H-E) was used to observe morphological changes in the liver, gallbladder, stomach, and colon tissues. Compared with the normal control group, both high-fat and capsicum diets significantly elevated blood lipid levels and inflammatory indexes in the serum of guinea pigs (P<0.01), with the effects being more pronounced in the high-fat diet group (P<0.001). Pathological results indicated that both high-fat and capsicum diets induce damage to the liver, stomach, gallbladder, and colon, with the high-fat diet showing particularly significant effects. Conclusion: Consuming high-fat and capsicum foods may induce damage to the digestive system, resulting in abnormal lipid metabolism. Health sciences/Gastroenterology/Gastrointestinal diseases/Nutrition disorders Health sciences/Medical research/Experimental models of disease Biological sciences/Physiology/Metabolism/Feeding behaviour/Obesity Biological sciences/Zoology/Animal physiology Health sciences/Pathogenesis/Infection Health sciences/Gastroenterology/Hepatology/Liver diseases/Liver fibrosis high-fat diet capsicum diet digestive organs lipid metabolism comparative medicine Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION The occurrence of human diseases is closely related to multiple factors, including dietary habits, climatic conditions, daily routines, infectious diseases, and unexpected events. It is widely believed that dietary habits are one of the critical factors leading to digestive system diseases. Humans supplement their energy by consuming proteins, lipids, dietary fibers, vitamins, and carbohydrates. Maintaining a healthy diet can positively affect the body's physiological functions, but improper dietary habits may adversely affect these functions, particularly those of the digestive system. For instance, studies have shown that long-term intake of high-fat and high-sugar foods can lead to metabolic imbalances in sugar and fat, potentially resulting in metabolic disorders such as hyperlipidemia and diabetes and causing damage to vital organs like the liver and stomach. To date, many scholars believe that consuming capsicum might effectively alleviate lipid metabolic disorders and improve symptoms of hyperlipidemia. Nevertheless, some scholars argue that eating capsicum may cause ulcerative damage to the gastrointestinal mucosa and, in extreme cases, increase the risk of gastrointestinal cancer. Therefore, although scholars have vastly different views on the consumption of capsicum, no research report has systematically observed the effects of a long-term Capsicum pepper diet on the morphological changes of digestive organs. Therefore, our research team conducted a study comparing the effects of high-fat and capsicum diets on guinea pigs' blood lipid indicators such as triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein, as well as the histomorphological impacts on critical digestive organs like the liver, stomach, gallbladder, and colon. This aims to provide scientific recommendations and guidance for a balanced diet.This study was conducted in accordance with the guidelines set forth by ARRIVE. 2. MATERIALS AND METHODS 2.1Materials 2.1.1Laboratory Animals and Feed We selected 24 male SPF-grade Hartly strain guinea pigs weighing 200 and 220g each, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (License No.: SCXK (Beijing) 2021-0011). All guinea pigs were housed in experimental animal rooms maintained at 20-24°C and humidity of 45%-55%, with a 12-hour light/dark cycle for one week of acclimatization. All animal experimental procedures strictly adhered to the Inner Mongolia Medical University Guidelines for the Care and Use of Laboratory Animals and have been formally approved by the Inner Mongolia Medical University Animal Ethics Committee (ethics approval number: YKD202302058). The feed and high-fat feed are purchased from Beijing Xiaoshu Youtai Company (license number:SCXK (Beijing) 2018-0006 ), while the Capsicum annuum var. conoides is sourced from Sichuan Honglin Food Co., Ltd. (license number: SC10351018201640). Beijing Xiaoshu Youtai Company manufactures the Capsicum annuum var. Conoides（Table1.）. Table 1. Information on Main Feed Ingredients Feed Name Ingredients Production Company Production License Number High-fat feed 78.85% basic feed + 21% lard + 0.15% cholesterol Xiaoshu Youtai (Beijing) Biotechnology Company SCXK (Beijing) 2018-0006 10% Capsicum annuum var. conoides content feed 10% Capsicum annuum var. conoides + 90% maintenance feed Xiaoshu Youtai (Beijing) Biotechnology Company SC10351018201640 2.1.2Main experimental reagents In this study, the primary reagents and instruments we used included biochemical reagent kits such as triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); ELISA kits for tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β）, and interleukin-6(IL-6）; and pathological morphology examination reagents such as 4% paraformaldehyde solution, ethanol solution, xylene solution, hematoxylin staining solution (Shanghai YuanYe Bio-Technology Co., Ltd.), and eosin staining solution (Shanghai YuanYe Bio-Technology Co., Ltd.). 2.2Methods 2.2.1Model preparation Twenty-four guinea pigs were randomly assigned to three different groups（Random grouping method by body weight）: the control group (C group，n=8), the high-fat diet group (HFD group，n=8), and the capsicum diet group (CD group，n=8). The specific model construction methods are as follows: a.We provided regular maintenance feed in the control group and did not create a model. b.We used high-fat feed to construct the model in the high-fat diet group. c.We used feed containing capsicum annuum var. conoides content feed in the capsicum diet group to construct the model. The preparation cycle for the model is 90 days. 2.2.2 Sample collection On the 91st day, we collected samples and administered sodium pentobarbital (45 mg/kg) via intraperitoneal injection for anesthesia. After anesthesia, the guinea pig was placed on a surgical table, subjected to an abdominal incision, and 5 milliliters of blood extracted from the abdominal aorta (using standard tubes for biochemical and enzyme-linked immunosorbent tests), spun at 3000 rpm in a slow centrifuge, and the supernatant obtained was stored in a freezer at -80°C. In this procedure, we initially secured the portal vein's root with forceps, severed the blood vessels and ligaments, extracted the liver, then the gallbladder, and moved it into a 10% paraformaldehyde solution for stabilization. Subsequently, we secured the guinea pigs stomach cardia using forceps, sliced the stomach along its more enormous curve with dissection scissors, washed its contents with saline, and immersed it in a 10% paraformaldehyde solution for stabilization. Finally, we cut the colon 5 cm distal to the ileocecal valve, rinsed the intestinal contents with saline, and transferred it into a 10% paraformaldehyde solution for fixation. 2.2.3 Serum Biochemical Analysis During this study, we conducted biochemical tests on the serum lipid levels of each group of guinea pigs. These indicators included triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The tests mentioned above were carried out strictly according to the reagent manufacturer's recommendations and in strict adherence to biochemical testing procedures and methods. 2.2.4 Enzyme-linked immunosorbent assay Spin the gathered blood sample at a speed of 3000 revolutions per minute for 20 minutes. Establish both standard and sample wells. Introduce 100 μL of a standard solution with different concentrations into the standard wells, followed by 40μL of the sample diluent in the wells, and subsequently, incorporate 10μL of the serum sample. Refrain from introducing any sample or enzyme reagent into the empty control wells. Except for the empty wells, introduce 50μL of enzyme reagent into every standard and sample well, secure the reaction wells using a sealing membrane, and maintain at seven °C in an incubator for half an hour. Remove the liquid and gently dry it. Insert the washing liquid into every well. Introduce 50μL of enzyme reagent into every standard and sample well, secure the reaction wells using a sealing membrane, and maintain at seven °C for half an hour. Remove the liquid, gently dry it, and then introduce the washing solution into each well. Following a 30-second interval, remove the liquid and perform this procedure five times, ensuring it is softly dried each time. Introduce 50μL of dye A into each well, then add 50μL of dye B. Carefully blend and let it sit in darkness at 37°C for 10 minutes to achieve the desired color. Introduce 50μL of the stop solution to halt the reaction in every well. Employ the empty wells for calibration to zero in 15 minutes, followed by sequentially measuring the absorbance (OD) at 450 nm for each well. 2.2.5 Histopathology Take 10% formaldehyde-fixed liver, stomach, gallbladder, and colon tissue samples, trim them, and place the wrapped tissue samples in 75% ethanol overnight. Then, dehydrate using 95% ethanol, followed by tissue clearing in xylene. Finally, place the cleared tissue samples in embedding molds filled with paraffin, soak for 3 hours, then embed, and cut into 5mm thickness. Lastly, stain the liver, stomach, gallbladder, and colon tissue sections with hematoxylin-eosin(HE), examine under a microscope, and take photographs. 2.2.6 Statistical Analysis The data was processed using SPSS 28.0 statistical software. A t-test or rank-sum test was used for comparisons between the two groups. The statistical results for each group were recorded as X±S. Statistical graphs were created using GraphPad 9.5 software. 3. RESULTS 3.1 The Effects of a High-Fat Diet and a Capsicum Diet on Lipid Indices in Guinea Pigs First, we used biochemical detection techniques to observe changes in blood lipid indicators such as TG, TC, HDL-C, and LDL-C in the serum of guinea pigs in each group. The study found that, compared to the C group, the HFD group showed significant increases in TG, TC, HDL-C, and LDL-C levels, with these increases being statistically significant (P<0.0001 ). Meanwhile, the CD group also showed significant increases in TG, TC, HDL-C, and LDL-C levels compared to the C group, with noticeable differences between these indicators ( P<0.01, P<0.0001, P<0.05, P<0.01 ). Compared to the HFD group, the increases in TG, TC, HDL-C, and LDL-C levels in the CD group were not as pronounced, with significant differences between these indicators ( P<0.0001 ). The above study indicates that consuming high-fat and capsicum diet significantly increases blood lipids in guinea pigs, with the effect of high-fat foods being particularly notable(Fig1.). 3.2The effects of a high-fat diet and a Capsicum diet on the inflammatory markers in serum of guinea pigs Secondly, we used enzyme-linked immunosorbent assay (ELISA) to observe the changes in inflammatory markers such as TNF-α, IL-1β, and IL-6 in the serum of guinea pigs from different groups. Through in-depth research, we observed that compared with the C group, the HFD group showed a significant increase in the values of TNF-α, IL-1β, and IL-6, with significant differences ( P <0.0001, P <0.001, P <0.0001). In the CD group, the values of TNF-α, IL-1β, and IL-6 also increased significantly, and there were obvious differences in these indicators compared with the C group ( P <0.01, P <0.05, P <0.0001). Compared to the HFD group, the increase in TNF-α, IL-1β, and IL-6 values in the CD group was not significant, but differences were found in the TNF-α and IL-6 values ( P <0.01, P 0.05). The above research results indicate that the intake of high-fat and capsicum diet significantly leads to serum inflammation in guinea pigs, with the effect being particularly notable for high-fat foods(Fig2.). 3.3The Effects of High-Fat Diet and Capsicum Diet on the Morphological Changes of Guinea Pig Liver, Stomach, Gallbladder, and Colon Tissues We employed Hematoxylin-Eosin staining (HE staining) techniques to slice and stain the liver, stomach, gallbladder, and colon tissues of guinea pigs. The experimental results indicated that, compared to the C group, the HFD group exhibited extensive hepatic steatosis in the liver tissue. Various sizes of round vacuoles (black arrows) were observed in the cytoplasm, with a slight proliferation of oval cells (yellow arrows), accompanied by mild fibrosis (blue arrows) and focal inflammatory cell infiltration (red arrows). In the liver tissues of the CD group, there was significant hepatic steatosis with small round vacuoles in the cytoplasm (black arrows), mild proliferation of oval cells (yellow arrows), and slight fibrosis around the portal area (blue arrows), but no obvious inflammatory cell infiltration was observed. The above study results suggest that consuming high-fat diet significantly exacerbates hepatic steatosis and leads to the occurrence of liver inflammatory responses. Although the intake of capsicum may cause hepatic steatosis, its damage to the liver is relatively mild compared to high-fat diet, and the inflammatory response is not evident(Fig3.). Compared to the C group, the HFD group showed irregular gastric gland morphology in the gastric mucosal layer, with punctate necrosis and shedding of gastric gland cells. Detached cellular debris was visible in the glandular lumen (orange arrow), with ulceration in the mucosal layer, atrophy, and necrosis of the gastric glands. The structure was replaced by proliferative connective tissue, with few residual glands of irregular shape (black arrow) and congestion in the stromal capillaries (green arrow), accompanied by significant inflammatory cell infiltration (red arrow). There was localized edema in the submucosal layer. In the gastric tissue of the CD group, localized ulcers and loss of mucosal epithelial structure were observed. In the lamina propria, gastric gland atrophy and necrosis were evident, with structures replaced by proliferative connective tissue and irregularly shaped residual glands (black arrow), showing cystic dilation (yellow arrow), along with inflammatory cell infiltration (red arrow). In the surrounding areas of the ulcerative lesions, small-scale edema of the lamina propria, gastric gland atrophy, and scattered inflammatory cell infiltration were also observed (blue arrow). The above study results indicate that the intake of high-fat diet and capsicum significantly exacerbates gastric mucosal ulcer damage, gastric gland atrophy and necrosis, and inflammatory responses(Fig3.). Compared to the C group, the gallbladder tissue of the HFD group showed mucosal layer atrophy and thinning, with many mucosal epithelial cells transforming from tall columnar epithelial cells to short columnar epithelial cells (black arrows), while the lamina propria showed no significant abnormalities and no obvious inflammatory cell infiltration. In the CD group, the gallbladder tissue showed mild mucosal layer atrophy and thinning, with a few mucosal epithelial cells transforming from tall columnar epithelial cells to short columnar epithelial cells (black arrows), and the lamina propria showed no significant abnormalities and no obvious inflammatory cell infiltration(Fig3.). Compared to the C group, the HFD group showed thinning of the intestinal wall in colon tissue, a reduction in the number of goblet cells (black arrow), scattered inflammatory cell infiltration in the lamina propria (red arrow), and a noticeable increase in fat cells in the submucosa (blue arrow). In the CD group, the colon tissue also exhibited a thinning of the intestinal wall, a reduction in the number of goblet cells (black arrow), lymphoid hyperplasia in the lamina propria and submucosa (yellow arrow), and a noticeable increase in fat cells in the submucosa (blue arrow)(Fig3.). 4. DISCUSSION Human health is related to various factors, including dietary habits(Ikeda & Collaborators, 2021; Przybylowicz & Danielewicz, 2022),environmental conditions(Beier & Arteel, 2021; Campbell-Lendrum & Woodruff, 2006), genetic factors(Nakanishi, Shimizu, Kumagai, Takai, & Marusawa, 2021), and more. Among these, nutritional factors are particularly crucial. People obtain the necessary nutrients for their bodies by consuming various foods, such as dietary proteins, lipids, cereal fibers, and vitamins, providing essential energy. Additionally, nutritional habits can also lead to human diseases, such as the prolonged consumption of certain specific foods. Studies have shown that long-term intake of high-fat foods may increase the risk of metabolic-related diseases such as obesity(Calder et al., 2011; Rasool, Geetha, Broderick, & Babu, 2018), hyperlipidemia(Bozzetto, Della Pepa, Vetrani, & Rivellese, 2020), and diabetes(Zhao et al., 2022). Interestingly, researchers have differing opinions on the effects of long-term capsicum consumption. Some scholars believe that eating capsicum long-term can burn body fat and energy(Shin, Yang, & Han, 2020). Therefore, most studies focus on the role of dietary capsicum or capsaicin in preventing and treating metabolic diseases(Panchal, Bliss, & Brown, 2018). However,some scholars argue that long-term capsicum consumption may harm the digestive system and, in extreme cases, may lead to health issues such as stomach and colon cancer(Chan et al., 2021; Chen et al., 2017). Despite the differing views on the potential impacts of long-term capsicum consumption, the specific mechanisms remain a mystery. The purpose and innovation of this study lie in comparing the effects of two different dietary patterns, high-fat diet and capsicum diet, on the histomorphology of the digestive system (including liver, stomach, gallbladder, and colon tissues). It aims to observe how long-term intake of these two dietary patterns affects the digestive organs. This study found that both high-fat diets and capsicum diets can potentially increase the levels of serum triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein in guinea pigs. This study found that long-term consumption of capsicum significantly leads to gastric mucosal ulcers, gastric gland atrophy, and necrosis, inducing gastritis. The stomach is responsible for storing food and achieving mechanical and chemical digestion through gastric motility, secretion of gastric acid, and pepsin. Factors such as the gastric mucosal barrier and gastric acid also help prevent the invasion of pathogens and foreign bodies. Previous extensive studies have shown that a high-fat diet significantly increases the incidence of gastritis. Additionally, studies have found that a high-fat diet increases the number of ghrelin-expressing cells in the stomach, leading to obesity(François et al., 2016; Sato et al., 2014; van Loenen, Geenen, Arnoldussen, & Kiliaan, 2022). This study found that the gastric mucosa in the high-fat diet group was significantly damaged, ulcerated, and accompanied by gastric tissue inflammation. The above studies indicate that a high-fat diet can indeed lead to the occurrence of gastritis and gastric ulcers. Previous research has confirmed that Capsicum peppers can damage gastrointestinal tissues and cause significant inflammation in the jejunum, ileum, and colon. Combining the research views of the above scholars, our research team believes that long-term consumption of a high-fat diet or capsicum diet may induce gastric tissue damage, thereby triggering gastritis and gastric ulcers. This study also confirms that long-term consumption of a high-fat diet can indeed lead to liver steatosis, fibrosis, and inflammatory responses, while long-term consumption of capsaicin can significantly cause liver steatosis and mild fibrosis, but the inflammatory changes are not significant. The liver is not only one of the main metabolic organs and digestive glands of the human body but also plays a key role in glucose and lipid metabolism and is responsible for the production and secretion of bile. Numerous research results confirm that long-term consumption of a high-fat diet can significantly lead to liver fat accumulation, liver fibrosis(Jia, Hu, Kimura, & Tanaka, 2021; Wu et al., 2008), and liver inflammation(Fonseca et al., 2020). Some scholars have confirmed that dietary capsaicin has potential benefits in treating cholestatic liver fibrosis and preventing hepatotoxic liver injury(Karimi-Sales, Mohaddes, & Alipour, 2024; Sheng, Zhang, Chen, & Yu, 2020). In addition, studies have shown that capsaicin inhibits liver fat accumulation in mice with non-alcoholic fatty liver disease induced by a high-fat diet(Shin et al., 2020). Other research has confirmed that capsaicin inhibits liver cancer by suppressing liver progenitor cells' stemness through the SIRT1/SOX2 signaling pathway(Xie et al., 2022). These studies suggest that dietary capsaicin may improve liver fibrosis, liver fat accumulation, and inhibit the occurrence of liver cancer. The above conclusions indicate that capsaicin has a positive effect on improving liver diseases. However, some studies have shown that the intake of different doses of capsaicin affects liver function differently. Specifically, doses of 5 mg·kg−1 and 15 mg·kg−1 of capsaicin are beneficial for liver digestive function and antioxidant capacity, while a dose of 20 mg·kg−1 of capsaicin is detrimental to liver digestive function and antioxidant capacity. Based on the conclusions of other scholars' research, our research team believes that both high-fat diets and capsaicin diets may induce liver tissue damage, leading to liver steatosis and fibrotic changes. In this study, it was found that high-fat and capsicum diets can lead to gallbladder mucosal atrophy. The gallbladder has functions of storing, concentrating, and emptying bile. Studies show that bile is also involved in the cholesterol metabolism process. Moderate fat intake stimulates the normal contraction of the gallbladder, allowing bile to be emptied in a timely manner, reducing bile stasis, and preventing gallstone formation and exacerbation of cholecystitis. However, long-term high-fat intake can weaken the gallbladder's contraction function(Kim et al., 2023; Mathur et al., 2008). Research has confirmed that a high-fat diet can significantly increase the formation of cholesterol stones(Di Ciaula et al., 2019; Parra-Landazury, Cordova-Gallardo, & Méndez-Sánchez, 2021). Additionally, studies have shown that the excessive consumption of red capsicum peppers has been proven to be a cancer risk factor in Chilean women with gallstones(Báez et al., 2010; Tsuchiya et al., 2011). Based on the viewpoints of the aforementioned scholars, our research team believes that both high-fat diets and capsicum pepper diets may lead to gallbladder mucosal atrophy and impaired gallbladder contraction function. This study found that both high-fat and capsicum diets can thin the colon tissue and induce inflammatory responses, while also causing a large number of fat cells to appear in the submucosa of the colon tissue. The colon plays a crucial role in the digestive system; it is not only the site for absorbing nutrients like vitamins, water, and inorganic salts, and for forming feces, but the bacteria and microorganisms in the colon also play a key role in maintaining the metabolic balance of the digestive system. Some scholars' research has confirmed that a high-fat diet induces oxidative stress in the colonic mucosa, which increases the permeability of the colonic epithelial barrier and triggers inflammation of the colonic mucosa(Li et al., 2019). Other studies have shown that long-term high intake of trans-unsaturated fatty acids is closely associated with an increased incidence of ulcerative colitis.According to the results of a study, the frequency of dietary chili diets is strongly associated with the incidence of colitis(Mi et al., 2022). Based on the viewpoints of the above-mentioned scholars, our research team believes that both high-fat and capsicum diets can cause damage to colon tissue and induce colitis. In summary, long-term consumption of a high-fat diet and a diet rich in capsicum peppers has negative effects on the tissues of digestive organs such as the liver, stomach, gallbladder, and colon. The shortcoming lies in the fact that the study only analyzed the tissue changes in digestive organs caused by a high-fat diet and a capsicum diet at the morphological level, without delving into the underlying mechanisms of related damage. 5. CONCLUSIONS This study indicates long-term high-fat or capsicum diet consumption may induce damage to major digestive organs such as the liver, stomach, gallbladder, and colon, resulting in lipid metabolism disorders. Declarations CONFLICT OF INTEREST The authors declare no conflict of interests. Wen-Xiang Guan and Zhuo Lan primarily conducted this study and wrote the paper, making equal contributions to the research. Wen-Xiang Guan is the first author, and Zhuo Lan is a co-first author. Wen-Xiang Guan and Xiao-Jun Luo primarily conducted the experimental procedures, and Zhuo Lan prepared Figures 1-3. Jing-Xian Gao and Chang-xi Bai supervised the experimental operations and manuscript writing, and all authors reviewed the manuscript. Jing-Xian Gao and Chang-Xi Bai made equal contributions to the writing and guidance of the experiments, with Chang-Xi Bai as the corresponding author and Jing-Xian Gao/Xiao-Jun Luo as the co-corresponding author. ACKNOWLEDGMENT This research was supported by several projects, including the Inner Mongolia Autonomous Region Science and Technology Project（Investigations into Mongolian medicinal practices have focused on the creation and application of bear bile substitutes, particularly their anti-diabetic and pancreatic regeneration properties）. Inner Mongolian Medical University's Mongolian Pharmaceutical "First Class Program" Project (MYX2022-K01), the Inner Mongolian Medical University's Mongolian Pharmaceutical "First Class Program" Graduate Research Capacity Enhancement Program (MYX2022-R08), the Inner Mongolian Medical University's Mongolian medicine "First Class Program" Graduate Research Innovation Program (2022 MYYLXKYC009), and the Inner Mongolian Coordinating Innovation's Mongolian Medical Research Center's Graduate Research Capacity Enhancement Program (MYXXTBS202309), and the Education Department of Inner Mongolia Autonomous Region Project (Biological Basis of Atherosclerotic Heat and Cold Classification-B20231119Z). ABOUT THE AUTHORS Wen-Xiang Guan , male, a doctoral student majoring in Ethnic Medicine (Mongolian Medicine) at Inner Mongolia Medical University, enrolled in 2021. Research direction is the fundamental theory of Mongolian Medicine. 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P., Zhang, B. H., Chen, Y. F., & Yu, F. X. (2020). Capsaicin attenuates liver fibrosis by targeting Notch signaling to inhibit TNF-α secretion from M1 macrophages. Immunopharmacology and Immunotoxicology, 42 (6), 556-563. doi:10.1080/08923973.2020.1811308 Shin, M. K., Yang, S. M., & Han, I. S. (2020). Capsaicin suppresses liver fat accumulation in high-fat diet-induced NAFLD mice. Animal Cells and Systems, 24 (4), 214-219. doi:10.1080/19768354.2020.1810771 Tsuchiya, Y., Terao, M., Okano, K., Nakamura, K., Oyama, M., Ikegami, K., & Yamamoto, M. (2011). Mutagenicity and Mutagens of the Red Chili Pepper as Gallbladder Cancer Risk Factor in Chilean Women. Asian Pacific Journal of Cancer Prevention, 12 (2), 471-476. Retrieved from ://WOS:000293172800025 van Loenen, M. R., Geenen, B., Arnoldussen, I. A. C., & Kiliaan, A. J. (2022). Ghrelin as a prominent endocrine factor in stress-induced obesity. Nutritional Neuroscience, 25 (7), 1413-1424. doi:10.1080/1028415x.2020.1863740 Wu, J., Liu, J., Waalkes, M. P., Cheng, M. L., Li, L., Li, C. X., & Yang, Q. (2008). High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Experimental Biology and Medicine, 233 (3), 377-384. doi:10.3181/0710-Rm-269 Xie, Z. Q., Li, H. X., Hou, X. J., Huang, M. Y., Zhu, Z. M., Wei, L. X., & Tang, C. X. (2022). Capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of hepatic progenitor cells via SIRT1/SOX2 signaling pathway. Cancer Medicine, 11 (22), 4283-4296. doi:10.1002/cam4.4777 Zhao, Y., Wang, Q. Y., Zeng, L. T., Wang, J. J., Liu, Z., Fan, G. Q., . . . Cai, J. P. (2022). Long-Term High-Fat High-Fructose Diet Induces Type 2 Diabetes in Rats through Oxidative Stress. Nutrients, 14 (11). doi:ARTN 218110.3390/nu14112181 Additional Declarations No competing interests reported. Supplementary Files Technologyroadmap.jpeg Cite Share Download PDF Status: Published Journal Publication published 23 May, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 30 Sep, 2024 Reviews received at journal 29 Sep, 2024 Reviews received at journal 22 Sep, 2024 Reviewers agreed at journal 19 Sep, 2024 Reviewers agreed at journal 19 Sep, 2024 Reviewers invited by journal 19 Sep, 2024 Editor assigned by journal 19 Sep, 2024 Editor invited by journal 29 Aug, 2024 Submission checks completed at journal 28 Aug, 2024 First submitted to journal 09 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4886822","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":357513862,"identity":"2a9cf926-99cb-45e6-a49c-a56a4488d9b7","order_by":0,"name":"Wen-Xiang Guan","email":"","orcid":"","institution":"Inner Mongolia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Xiang","middleName":"","lastName":"Guan","suffix":""},{"id":357513863,"identity":"0a62ea7a-8c42-490d-b9f0-899c7d7d0276","order_by":1,"name":"Zhuo Lan","email":"","orcid":"","institution":"Inner Mongolia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhuo","middleName":"","lastName":"Lan","suffix":""},{"id":357513864,"identity":"f71c4cba-d74e-4559-bcb2-26a15ccaaad1","order_by":2,"name":"Xiao-Jun Luo","email":"","orcid":"","institution":"Hulunbuir City Chinese-Mongolian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiao-Jun","middleName":"","lastName":"Luo","suffix":""},{"id":357513865,"identity":"e49108e5-89cb-441c-822f-13a2fc90be3d","order_by":3,"name":"Jing-Xian Gao","email":"","orcid":"","institution":"Inner Mongolia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing-Xian","middleName":"","lastName":"Gao","suffix":""},{"id":357513866,"identity":"4b8e99c6-cedc-4cf0-82df-a17ce0974f19","order_by":4,"name":"Chang-xi Bai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYBACAyA+8KGCjYeNvf3ggwSEIF4tjAdnnOGT4+c5k2xArBbmw7xtcsaSMxzMJBiI0WLOfsYAqMUsccMNhrSKhznbEhvYm7dJMNTcwanFsict4eCcc2mJG243HruRuO12YgPPsTIJhmPPcDvsBvOBA2/KjiVuuHMgDaJFIsdMgrHhMB4tjA0HeNj+Ax2WYFYA1iL/hpAW5gMHedrYgN5PMGOA2MKDXwvYLzPOsIEDWQKoxbiNJ63YIuEYbi3AEDP+AIvKjz+33ZbtZz+88caHGtxaMAEbiEggQcMoGAWjYBSMAkwAAKqCYYVIRZ+gAAAAAElFTkSuQmCC","orcid":"","institution":"Inner Mongolia Medical University","correspondingAuthor":true,"prefix":"","firstName":"Chang-xi","middleName":"","lastName":"Bai","suffix":""}],"badges":[],"createdAt":"2024-08-09 11:44:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4886822/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4886822/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-93583-4","type":"published","date":"2025-05-23T15:58:19+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":65435578,"identity":"60ec410f-2be8-4b94-a86c-3406282471f6","added_by":"auto","created_at":"2024-09-27 12:12:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":210685,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of high-fat diet and capsicum diet on serum lipids in guinea pigs. Compared with the control group, \u003cem\u003e* P\u0026lt;0.05, ** P\u0026lt;0.01, *** P\u0026lt;0.001, **** P\u0026lt;0.0001\u003c/em\u003e. Compared to the high-fat diet group, \u003cem\u003e# P\u0026lt;0.05, ## P\u0026lt;0.01, ### P\u0026lt;0.001, #### P\u0026lt;0.0001\u003c/em\u003e；N=8.\u003c/p\u003e","description":"","filename":"Fig1..png","url":"https://assets-eu.researchsquare.com/files/rs-4886822/v1/00bc7cf6980d94b6b38ece7f.png"},{"id":65435422,"identity":"07557a7b-01a7-41a7-baf3-b18709d3619b","added_by":"auto","created_at":"2024-09-27 12:12:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":160773,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of high-fat diet and capsicum diet on the inflammatory markers in serum of guinea pig. Compared with the control group, \u003cem\u003e* P\u0026lt;\u003c/em\u003e0.05\u003cem\u003e, ** P\u0026lt;\u003c/em\u003e0.01\u003cem\u003e, *** P\u0026lt;\u003c/em\u003e0.001\u003cem\u003e, **** P\u0026lt;\u003c/em\u003e0.0001. Compared to the high-fat diet group, # P\u0026lt;0.05, ## P\u0026lt;0.01, ### P\u0026lt;0.001, #### P\u0026lt;0.0001；N=8.\u003c/p\u003e","description":"","filename":"Fig2..png","url":"https://assets-eu.researchsquare.com/files/rs-4886822/v1/63177051376f280407dcb485.png"},{"id":65435550,"identity":"d45f196b-b14c-492b-82d9-942f5bcc08df","added_by":"auto","created_at":"2024-09-27 12:12:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":5662953,"visible":true,"origin":"","legend":"\u003cp\u003eshows the pathological morphological changes in the digestive organs such as the liver, stomach, gallbladder, and colon of guinea pigs in each group. All pathological slide results are expressed at ×100 magnification.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4886822/v1/2f4e202eb2ba6e6d43b6a505.png"},{"id":83460110,"identity":"925ec472-5020-4f77-831e-4c2fc6300700","added_by":"auto","created_at":"2025-05-26 16:10:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7690359,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4886822/v1/25d6d955-3926-4c93-a947-41237e09d32e.pdf"},{"id":65435518,"identity":"50da1581-04f9-48bc-b04b-4b33ead063aa","added_by":"auto","created_at":"2024-09-27 12:12:12","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2532717,"visible":true,"origin":"","legend":"","description":"","filename":"Technologyroadmap.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4886822/v1/77693ab398b21b7711f53fa8.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Study on the Effects of High-Fat Diet and Capsicum Diet on the Digestive Organs of Guinea Pigs","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eThe occurrence of human diseases is closely related to multiple factors, including dietary habits, climatic conditions, daily routines, infectious diseases, and unexpected events. It is widely believed that dietary habits are one of the critical factors leading to digestive system diseases. Humans supplement their energy by consuming proteins, lipids, dietary fibers, vitamins, and carbohydrates. Maintaining a healthy diet can positively affect the body's physiological functions, but improper dietary habits may adversely affect these functions, particularly those of the digestive system. For instance, studies have shown that long-term intake of high-fat and high-sugar foods can lead to metabolic imbalances in sugar and fat, potentially resulting in metabolic disorders such as hyperlipidemia and diabetes and causing damage to vital organs like the liver and stomach. To date, many scholars believe that consuming capsicum might effectively alleviate lipid metabolic disorders and improve symptoms of hyperlipidemia. Nevertheless, some scholars argue that eating capsicum may cause ulcerative damage to the gastrointestinal mucosa and, in extreme cases, increase the risk of gastrointestinal cancer. Therefore, although scholars have vastly different views on the consumption of capsicum, no research report has systematically observed the effects of a long-term Capsicum pepper diet on the morphological changes of digestive organs.\u003c/p\u003e\n\u003cp\u003eTherefore, our research team conducted a study comparing the effects of high-fat and capsicum diets on guinea pigs' blood lipid indicators such as triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein, as well as the histomorphological impacts on critical digestive organs like the liver, stomach, gallbladder, and colon. This aims to provide scientific recommendations and guidance for a balanced diet.This study was conducted in accordance with the guidelines set forth by ARRIVE.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003e2.1Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.1Laboratory Animals and Feed\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe selected 24 male SPF-grade Hartly strain guinea pigs weighing 200 and 220g each, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (License No.: SCXK (Beijing) 2021-0011). All guinea pigs were housed in experimental animal rooms maintained at 20-24\u0026deg;C and humidity of 45%-55%, with a 12-hour light/dark cycle for one week of acclimatization. All animal experimental procedures strictly adhered to the Inner Mongolia Medical University Guidelines for the Care and Use of Laboratory Animals and have been formally approved by the Inner Mongolia Medical University Animal Ethics Committee (ethics approval number: YKD202302058).\u003c/p\u003e\n\u003cp\u003eThe feed and high-fat feed are purchased from Beijing Xiaoshu Youtai Company (license number:SCXK (Beijing) 2018-0006 ), while the Capsicum annuum var. conoides is sourced from Sichuan Honglin Food Co., Ltd. (license number: SC10351018201640). Beijing Xiaoshu Youtai Company manufactures the Capsicum annuum var. Conoides（Table1.）.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Information on Main Feed Ingredients\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"578\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.584055459272097%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFeed Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.16984402079723%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIngredients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.303292894280762%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProduction Company\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.942807625649912%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProduction License Number\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.584055459272097%\"\u003e\n \u003cp\u003eHigh-fat feed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.16984402079723%\"\u003e\n \u003cp\u003e78.85% basic feed + 21% lard + 0.15% cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.303292894280762%\"\u003e\n \u003cp\u003eXiaoshu Youtai (Beijing) Biotechnology Company\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.942807625649912%\"\u003e\n \u003cp\u003eSCXK (Beijing) 2018-0006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.584055459272097%\"\u003e\n \u003cp\u003e10% Capsicum annuum var. conoides content feed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.16984402079723%\"\u003e\n \u003cp\u003e10% Capsicum annuum var. conoides + 90% maintenance feed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.303292894280762%\"\u003e\n \u003cp\u003eXiaoshu Youtai (Beijing) Biotechnology Company\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.942807625649912%\"\u003e\n \u003cp\u003eSC10351018201640\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\u003e\u003cstrong\u003e2.1.2Main experimental reagents\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, the primary reagents and instruments we used included biochemical reagent kits such as triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); ELISA kits for tumor necrosis factor-\u0026alpha; (TNF-\u0026alpha;), interleukin-1\u0026beta;(IL-1\u0026beta;）, and interleukin-6(IL-6）; and pathological morphology examination reagents such as 4% paraformaldehyde solution, ethanol solution, xylene solution, hematoxylin staining solution (Shanghai YuanYe Bio-Technology Co., Ltd.), and eosin staining solution (Shanghai YuanYe Bio-Technology Co., Ltd.).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.1Model preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwenty-four guinea pigs were randomly assigned to three different groups（Random grouping method by body weight）: the control group (C group，n=8), the high-fat diet group (HFD group，n=8), and the capsicum diet group (CD group，n=8). The specific model construction methods are as follows: a.We provided regular maintenance feed in the control group and did not create a model. b.We used high-fat feed to construct the model in the high-fat diet group. c.We used feed containing capsicum annuum var. conoides content feed in the capsicum diet group to construct the model. The preparation cycle for the model is 90 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.2 Sample collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the 91st day, we collected samples and administered sodium pentobarbital (45 mg/kg) via intraperitoneal injection for anesthesia. After anesthesia, the guinea pig was placed on a surgical table, subjected to an abdominal incision, and 5 milliliters of blood extracted from the abdominal aorta (using standard tubes for biochemical and enzyme-linked immunosorbent tests), spun at 3000 rpm in a slow centrifuge, and the supernatant obtained was stored in a freezer at -80\u0026deg;C. In this procedure, we initially secured the portal vein\u0026apos;s root with forceps, severed the blood vessels and ligaments, extracted the liver, then the gallbladder, and moved it into a 10% paraformaldehyde solution for stabilization. Subsequently, we secured the guinea pigs stomach cardia using forceps, sliced the stomach along its more enormous curve with dissection scissors, washed its contents with saline, and immersed it in a 10% paraformaldehyde solution for stabilization. Finally, we cut the colon 5 cm distal to the ileocecal valve, rinsed the intestinal contents with saline, and transferred it into a 10% paraformaldehyde solution for fixation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.3 Serum Biochemical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring this study, we conducted biochemical tests on the serum lipid levels of each group of guinea pigs. These indicators included triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The tests mentioned above were carried out strictly according to the reagent manufacturer\u0026apos;s recommendations and in strict adherence to biochemical testing procedures and methods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.4 Enzyme-linked immunosorbent assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpin the gathered blood sample at a speed of 3000 revolutions per minute for 20 minutes. Establish both standard and sample wells. Introduce 100 \u0026mu;L of a standard solution with different concentrations into the standard wells, followed by 40\u0026mu;L of the sample diluent in the wells, and subsequently, incorporate 10\u0026mu;L of the serum sample. Refrain from introducing any sample or enzyme reagent into the empty control wells. Except for the empty wells, introduce 50\u0026mu;L of enzyme reagent into every standard and sample well, secure the reaction wells using a sealing membrane, and maintain at seven \u0026deg;C in an incubator for half an hour. Remove the liquid and gently dry it. Insert the washing liquid into every well. Introduce 50\u0026mu;L of enzyme reagent into every standard and sample well, secure the reaction wells using a sealing membrane, and maintain at seven \u0026deg;C for half an hour. Remove the liquid, gently dry it, and then introduce the washing solution into each well. Following a 30-second interval, remove the liquid and perform this procedure five times, ensuring it is softly dried each time. Introduce 50\u0026mu;L of dye A into each well, then add 50\u0026mu;L of dye B. Carefully blend and let it sit in darkness at 37\u0026deg;C for 10 minutes to achieve the desired color. Introduce 50\u0026mu;L of the stop solution to halt the reaction in every well. Employ the empty wells for calibration to zero in 15 minutes, followed by sequentially measuring the absorbance (OD) at 450 nm for each well.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.5 Histopathology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTake 10% formaldehyde-fixed liver, stomach, gallbladder, and colon tissue samples, trim them, and place the wrapped tissue samples in 75% ethanol overnight. Then, dehydrate using 95% ethanol, followed by tissue clearing in xylene. Finally, place the cleared tissue samples in embedding molds filled with paraffin, soak for 3 hours, then embed, and cut into 5mm thickness. Lastly, stain the liver, stomach, gallbladder, and colon tissue sections with hematoxylin-eosin(HE), examine under a microscope, and take photographs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.6 Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data was processed using SPSS 28.0 statistical software. A t-test or rank-sum test was used for comparisons between the two groups. The statistical results for each group were recorded as X\u0026plusmn;S. Statistical graphs were created using GraphPad 9.5 software.\u003c/p\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003e\u003cstrong\u003e3.1 The Effects of a High-Fat Diet and a Capsicum Diet on Lipid Indices in Guinea Pigs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst, we used biochemical detection techniques to observe changes in blood lipid indicators such as TG, TC, HDL-C, and LDL-C in the serum of guinea pigs in each group. The study found that, compared to the C group, the HFD group showed significant increases in TG, TC, HDL-C, and LDL-C levels, with these increases being statistically significant \u003cem\u003e(P\u0026lt;0.0001\u003c/em\u003e). Meanwhile, the CD group also showed significant increases in TG, TC, HDL-C, and LDL-C levels compared to the C group, with noticeable differences between these indicators (\u003cem\u003eP\u0026lt;0.01, P\u0026lt;0.0001, P\u0026lt;0.05, P\u0026lt;0.01\u003c/em\u003e). Compared to the HFD group, the increases in TG, TC, HDL-C, and LDL-C levels in the CD group were not as pronounced, with significant differences between these indicators (\u003cem\u003eP\u0026lt;0.0001\u003c/em\u003e). The above study indicates that consuming high-fat and capsicum diet significantly increases blood lipids in guinea pigs, with the effect of high-fat foods being particularly notable(Fig1.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2The effects of a high-fat diet and a Capsicum diet on the inflammatory markers in serum of guinea pigs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSecondly, we used enzyme-linked immunosorbent assay (ELISA) to observe the changes in inflammatory markers such as TNF-α, IL-1β, and IL-6 in the serum of guinea pigs from different groups. Through in-depth research, we observed that compared with the C group, the HFD group showed a significant increase in the values of TNF-α, IL-1β, and IL-6, with significant differences (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001). In the CD group, the values of TNF-α, IL-1β, and IL-6 also increased significantly, and there were obvious differences in these indicators compared with the C group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001). Compared to the HFD group, the increase in TNF-α, IL-1β, and IL-6 values in the CD group was not significant, but differences were found in the TNF-α and IL-6 values (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), while there was no difference in the IL-1β value (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). The above research results indicate that the intake of high-fat and capsicum diet significantly leads to serum inflammation in guinea pigs, with the effect being particularly notable for high-fat foods(Fig2.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3The Effects of High-Fat Diet and Capsicum Diet on the Morphological Changes of Guinea Pig Liver, Stomach, Gallbladder, and Colon Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe employed Hematoxylin-Eosin staining (HE staining) techniques to slice and stain the liver, stomach, gallbladder, and colon tissues of guinea pigs. The experimental results indicated that, compared to the C group, the HFD group exhibited extensive hepatic steatosis in the liver tissue. Various sizes of round vacuoles (black arrows) were observed in the cytoplasm, with a slight proliferation of oval cells (yellow arrows), accompanied by mild fibrosis (blue arrows) and focal inflammatory cell infiltration (red arrows). In the liver tissues of the CD group, there was significant hepatic steatosis with small round vacuoles in the cytoplasm (black arrows), mild proliferation of oval cells (yellow arrows), and slight fibrosis around the portal area (blue arrows), but no obvious inflammatory cell infiltration was observed. The above study results suggest that consuming high-fat diet significantly exacerbates hepatic steatosis and leads to the occurrence of liver inflammatory responses. Although the intake of capsicum may cause hepatic steatosis, its damage to the liver is relatively mild compared to high-fat diet, and the inflammatory response is not evident(Fig3.).\u003c/p\u003e\n\u003cp\u003eCompared to the C group, the HFD group showed irregular gastric gland morphology in the gastric mucosal layer, with punctate necrosis and shedding of gastric gland cells. Detached cellular debris was visible in the glandular lumen (orange arrow), with ulceration in the mucosal layer, atrophy, and necrosis of the gastric glands. The structure was replaced by proliferative connective tissue, with few residual glands of irregular shape (black arrow) and congestion in the stromal capillaries (green arrow), accompanied by significant inflammatory cell infiltration (red arrow). There was localized edema in the submucosal layer. In the gastric tissue of the CD group, localized ulcers and loss of mucosal epithelial structure were observed. In the lamina propria, gastric gland atrophy and necrosis were evident, with structures replaced by proliferative connective tissue and irregularly shaped residual glands (black arrow), showing cystic dilation (yellow arrow), along with inflammatory cell infiltration (red arrow). In the surrounding areas of the ulcerative lesions, small-scale edema of the lamina propria, gastric gland atrophy, and scattered inflammatory cell infiltration were also observed (blue arrow). The above study results indicate that the intake of high-fat diet and capsicum significantly exacerbates gastric mucosal ulcer damage, gastric gland atrophy and necrosis, and inflammatory responses(Fig3.).\u003c/p\u003e\n\u003cp\u003eCompared to the C group, the gallbladder tissue of the HFD group showed mucosal layer atrophy and thinning, with many mucosal epithelial cells transforming from tall columnar epithelial cells to short columnar epithelial cells (black arrows), while the lamina propria showed no significant abnormalities and no obvious inflammatory cell infiltration. In the CD group, the gallbladder tissue showed mild mucosal layer atrophy and thinning, with a few mucosal epithelial cells transforming from tall columnar epithelial cells to short columnar epithelial cells (black arrows), and the lamina propria showed no significant abnormalities and no obvious inflammatory cell infiltration(Fig3.).\u003c/p\u003e\n\u003cp\u003eCompared to the C group, the HFD group showed thinning of the intestinal wall in colon tissue, a reduction in the number of goblet cells (black arrow), scattered inflammatory cell infiltration in the lamina propria (red arrow), and a noticeable increase in fat cells in the submucosa (blue arrow). In the CD group, the colon tissue also exhibited a thinning of the intestinal wall, a reduction in the number of goblet cells (black arrow), lymphoid hyperplasia in the lamina propria and submucosa (yellow arrow), and a noticeable increase in fat cells in the submucosa (blue arrow)(Fig3.).\u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eHuman health is related to various factors, including dietary habits(Ikeda \u0026amp; Collaborators, 2021; Przybylowicz \u0026amp; Danielewicz, 2022),environmental conditions(Beier \u0026amp; Arteel, 2021; Campbell-Lendrum \u0026amp; Woodruff, 2006), genetic factors(Nakanishi, Shimizu, Kumagai, Takai, \u0026amp; Marusawa, 2021), and more. Among these, nutritional factors are particularly crucial. People obtain the necessary nutrients for their bodies by consuming various foods, such as dietary proteins, lipids, cereal fibers, and vitamins, providing essential energy. Additionally, nutritional habits can also lead to human diseases, such as the prolonged consumption of certain specific foods. Studies have shown that long-term intake of high-fat foods may increase the risk of metabolic-related diseases such as obesity(Calder et al., 2011; Rasool, Geetha, Broderick, \u0026amp; Babu, 2018), hyperlipidemia(Bozzetto, Della Pepa, Vetrani, \u0026amp; Rivellese, 2020), and diabetes(Zhao et al., 2022). Interestingly, researchers have differing opinions on the effects of long-term capsicum consumption. Some scholars believe that eating capsicum long-term can burn body fat and energy(Shin, Yang, \u0026amp; Han, 2020). Therefore, most studies focus on the role of dietary capsicum or capsaicin in preventing and treating metabolic diseases(Panchal, Bliss, \u0026amp; Brown, 2018). However,some scholars argue that long-term capsicum consumption may harm the digestive system and, in extreme cases, may lead to health issues such as stomach and colon cancer(Chan et al., 2021; Chen et al., 2017). Despite the differing views on the potential impacts of long-term capsicum consumption, the specific mechanisms remain a mystery.\u003c/p\u003e \u003cp\u003eThe purpose and innovation of this study lie in comparing the effects of two different dietary patterns, high-fat diet and capsicum diet, on the histomorphology of the digestive system (including liver, stomach, gallbladder, and colon tissues). It aims to observe how long-term intake of these two dietary patterns affects the digestive organs.\u003c/p\u003e \u003cp\u003eThis study found that both high-fat diets and capsicum diets can potentially increase the levels of serum triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein in guinea pigs.\u003c/p\u003e \u003cp\u003eThis study found that long-term consumption of capsicum significantly leads to gastric mucosal ulcers, gastric gland atrophy, and necrosis, inducing gastritis. The stomach is responsible for storing food and achieving mechanical and chemical digestion through gastric motility, secretion of gastric acid, and pepsin. Factors such as the gastric mucosal barrier and gastric acid also help prevent the invasion of pathogens and foreign bodies. Previous extensive studies have shown that a high-fat diet significantly increases the incidence of gastritis. Additionally, studies have found that a high-fat diet increases the number of ghrelin-expressing cells in the stomach, leading to obesity(Fran\u0026ccedil;ois et al., 2016; Sato et al., 2014; van Loenen, Geenen, Arnoldussen, \u0026amp; Kiliaan, 2022). This study found that the gastric mucosa in the high-fat diet group was significantly damaged, ulcerated, and accompanied by gastric tissue inflammation. The above studies indicate that a high-fat diet can indeed lead to the occurrence of gastritis and gastric ulcers. Previous research has confirmed that Capsicum peppers can damage gastrointestinal tissues and cause significant inflammation in the jejunum, ileum, and colon. Combining the research views of the above scholars, our research team believes that long-term consumption of a high-fat diet or capsicum diet may induce gastric tissue damage, thereby triggering gastritis and gastric ulcers.\u003c/p\u003e \u003cp\u003eThis study also confirms that long-term consumption of a high-fat diet can indeed lead to liver steatosis, fibrosis, and inflammatory responses, while long-term consumption of capsaicin can significantly cause liver steatosis and mild fibrosis, but the inflammatory changes are not significant. The liver is not only one of the main metabolic organs and digestive glands of the human body but also plays a key role in glucose and lipid metabolism and is responsible for the production and secretion of bile. Numerous research results confirm that long-term consumption of a high-fat diet can significantly lead to liver fat accumulation, liver fibrosis(Jia, Hu, Kimura, \u0026amp; Tanaka, 2021; Wu et al., 2008), and liver inflammation(Fonseca et al., 2020). Some scholars have confirmed that dietary capsaicin has potential benefits in treating cholestatic liver fibrosis and preventing hepatotoxic liver injury(Karimi-Sales, Mohaddes, \u0026amp; Alipour, 2024; Sheng, Zhang, Chen, \u0026amp; Yu, 2020). In addition, studies have shown that capsaicin inhibits liver fat accumulation in mice with non-alcoholic fatty liver disease induced by a high-fat diet(Shin et al., 2020). Other research has confirmed that capsaicin inhibits liver cancer by suppressing liver progenitor cells' stemness through the SIRT1/SOX2 signaling pathway(Xie et al., 2022). These studies suggest that dietary capsaicin may improve liver fibrosis, liver fat accumulation, and inhibit the occurrence of liver cancer. The above conclusions indicate that capsaicin has a positive effect on improving liver diseases. However, some studies have shown that the intake of different doses of capsaicin affects liver function differently. Specifically, doses of 5 mg\u0026middot;kg\u0026minus;1 and 15 mg\u0026middot;kg\u0026minus;1 of capsaicin are beneficial for liver digestive function and antioxidant capacity, while a dose of 20 mg\u0026middot;kg\u0026minus;1 of capsaicin is detrimental to liver digestive function and antioxidant capacity. Based on the conclusions of other scholars' research, our research team believes that both high-fat diets and capsaicin diets may induce liver tissue damage, leading to liver steatosis and fibrotic changes.\u003c/p\u003e \u003cp\u003eIn this study, it was found that high-fat and capsicum diets can lead to gallbladder mucosal atrophy. The gallbladder has functions of storing, concentrating, and emptying bile. Studies show that bile is also involved in the cholesterol metabolism process. Moderate fat intake stimulates the normal contraction of the gallbladder, allowing bile to be emptied in a timely manner, reducing bile stasis, and preventing gallstone formation and exacerbation of cholecystitis. However, long-term high-fat intake can weaken the gallbladder's contraction function(Kim et al., 2023; Mathur et al., 2008). Research has confirmed that a high-fat diet can significantly increase the formation of cholesterol stones(Di Ciaula et al., 2019; Parra-Landazury, Cordova-Gallardo, \u0026amp; M\u0026eacute;ndez-S\u0026aacute;nchez, 2021). Additionally, studies have shown that the excessive consumption of red capsicum peppers has been proven to be a cancer risk factor in Chilean women with gallstones(B\u0026aacute;ez et al., 2010; Tsuchiya et al., 2011). Based on the viewpoints of the aforementioned scholars, our research team believes that both high-fat diets and capsicum pepper diets may lead to gallbladder mucosal atrophy and impaired gallbladder contraction function.\u003c/p\u003e \u003cp\u003eThis study found that both high-fat and capsicum diets can thin the colon tissue and induce inflammatory responses, while also causing a large number of fat cells to appear in the submucosa of the colon tissue. The colon plays a crucial role in the digestive system; it is not only the site for absorbing nutrients like vitamins, water, and inorganic salts, and for forming feces, but the bacteria and microorganisms in the colon also play a key role in maintaining the metabolic balance of the digestive system. Some scholars' research has confirmed that a high-fat diet induces oxidative stress in the colonic mucosa, which increases the permeability of the colonic epithelial barrier and triggers inflammation of the colonic mucosa(Li et al., 2019). Other studies have shown that long-term high intake of trans-unsaturated fatty acids is closely associated with an increased incidence of ulcerative colitis.According to the results of a study, the frequency of dietary chili diets is strongly associated with the incidence of colitis(Mi et al., 2022). Based on the viewpoints of the above-mentioned scholars, our research team believes that both high-fat and capsicum diets can cause damage to colon tissue and induce colitis.\u003c/p\u003e \u003cp\u003eIn summary, long-term consumption of a high-fat diet and a diet rich in capsicum peppers has negative effects on the tissues of digestive organs such as the liver, stomach, gallbladder, and colon.\u003c/p\u003e \u003cp\u003eThe shortcoming lies in the fact that the study only analyzed the tissue changes in digestive organs caused by a high-fat diet and a capsicum diet at the morphological level, without delving into the underlying mechanisms of related damage.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003eThis study indicates long-term high-fat or capsicum diet consumption may induce damage to major digestive organs such as the liver, stomach, gallbladder, and colon, resulting in lipid metabolism disorders.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWen-Xiang Guan and Zhuo Lan primarily conducted this study and wrote the paper, making equal contributions to the research. Wen-Xiang Guan is the first author, and Zhuo Lan is a co-first author. Wen-Xiang Guan and Xiao-Jun Luo primarily conducted the experimental procedures, and Zhuo Lan prepared Figures 1-3. Jing-Xian Gao and Chang-xi Bai supervised the experimental operations and manuscript writing, and all authors reviewed the manuscript. Jing-Xian Gao and Chang-Xi Bai made equal contributions to the writing and guidance of the experiments, with Chang-Xi Bai as the corresponding author and Jing-Xian Gao/Xiao-Jun Luo as the co-corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by several projects, including the Inner Mongolia Autonomous Region Science and Technology Project（Investigations into Mongolian medicinal practices have focused on the creation and application of bear bile substitutes, particularly their anti-diabetic and pancreatic regeneration properties）. Inner Mongolian Medical University's Mongolian Pharmaceutical \"First Class Program\" Project (MYX2022-K01), the Inner Mongolian Medical University's Mongolian Pharmaceutical \"First Class Program\" Graduate Research Capacity Enhancement Program (MYX2022-R08), the Inner Mongolian Medical University's Mongolian medicine \"First Class Program\" Graduate Research Innovation Program (2022 MYYLXKYC009), and the Inner Mongolian Coordinating Innovation's Mongolian Medical Research Center's Graduate Research Capacity Enhancement Program (MYXXTBS202309), and the Education Department of Inner Mongolia Autonomous Region Project (Biological Basis of Atherosclerotic Heat and Cold Classification-B20231119Z).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eABOUT THE AUTHORS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWen-Xiang Guan\u003c/strong\u003e, male, a doctoral student majoring in Ethnic Medicine (Mongolian Medicine) at Inner Mongolia Medical University, enrolled in 2021. Research direction is the fundamental theory of Mongolian Medicine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChang-Xi Bai\u003c/strong\u003e, male, Doctor of Medicine, Postdoctoral researcher, professor at Inner Mongolia Medical University, doctoral supervisor. Research focus: 1. Modernization and application research of Mongolian Medicine (Traditional Chinese Medicine) 2. Study of disease (molecular) pathogenesis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eB\u0026aacute;ez, S., Tsuchiya, Y., Calvo, A., Pruyas, M., Nakamura, K., Kiyohara, C., . . . Yamamoto, M. (2010). Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. \u003cem\u003eWorld Journal of Gastroenterology, 16\u003c/em\u003e(3), 372-378. doi:10.3748/wjg.v16.i3.372\u003c/li\u003e\n \u003cli\u003eBeier, J. I., \u0026amp; Arteel, G. E. (2021). 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Capsaicin attenuates liver fibrosis by targeting Notch signaling to inhibit TNF-\u0026alpha; secretion from M1 macrophages. \u003cem\u003eImmunopharmacology and Immunotoxicology, 42\u003c/em\u003e(6), 556-563. doi:10.1080/08923973.2020.1811308\u003c/li\u003e\n \u003cli\u003eShin, M. K., Yang, S. M., \u0026amp; Han, I. S. (2020). Capsaicin suppresses liver fat accumulation in high-fat diet-induced NAFLD mice. \u003cem\u003eAnimal Cells and Systems, 24\u003c/em\u003e(4), 214-219. doi:10.1080/19768354.2020.1810771\u003c/li\u003e\n \u003cli\u003eTsuchiya, Y., Terao, M., Okano, K., Nakamura, K., Oyama, M., Ikegami, K., \u0026amp; Yamamoto, M. (2011). Mutagenicity and Mutagens of the Red Chili Pepper as Gallbladder Cancer Risk Factor in Chilean Women. \u003cem\u003eAsian Pacific Journal of Cancer Prevention, 12\u003c/em\u003e(2), 471-476. Retrieved from \u0026lt;Go to ISI\u0026gt;://WOS:000293172800025\u003c/li\u003e\n \u003cli\u003evan Loenen, M. R., Geenen, B., Arnoldussen, I. A. C., \u0026amp; Kiliaan, A. J. (2022). Ghrelin as a prominent endocrine factor in stress-induced obesity. \u003cem\u003eNutritional Neuroscience, 25\u003c/em\u003e(7), 1413-1424. doi:10.1080/1028415x.2020.1863740\u003c/li\u003e\n \u003cli\u003eWu, J., Liu, J., Waalkes, M. P., Cheng, M. L., Li, L., Li, C. X., \u0026amp; Yang, Q. (2008). High dietary fat exacerbates arsenic-induced liver fibrosis in mice. \u003cem\u003eExperimental Biology and Medicine, 233\u003c/em\u003e(3), 377-384. doi:10.3181/0710-Rm-269\u003c/li\u003e\n \u003cli\u003eXie, Z. Q., Li, H. X., Hou, X. J., Huang, M. Y., Zhu, Z. M., Wei, L. X., \u0026amp; Tang, C. X. (2022). Capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of hepatic progenitor cells via SIRT1/SOX2 signaling pathway. \u003cem\u003eCancer Medicine, 11\u003c/em\u003e(22), 4283-4296. doi:10.1002/cam4.4777\u003c/li\u003e\n \u003cli\u003eZhao, Y., Wang, Q. Y., Zeng, L. T., Wang, J. J., Liu, Z., Fan, G. Q., . . . Cai, J. P. (2022). Long-Term High-Fat High-Fructose Diet Induces Type 2 Diabetes in Rats through Oxidative Stress. \u003cem\u003eNutrients, 14\u003c/em\u003e(11). doi:ARTN 218110.3390/nu14112181\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"high-fat diet, capsicum diet, digestive organs, lipid metabolism, comparative medicine","lastPublishedDoi":"10.21203/rs.3.rs-4886822/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4886822/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eResearch Objective: To clarify the different effects of high-fat diet and capsicum diet on the digestive organs of guinea pigs.\u003cstrong\u003e \u003c/strong\u003eExperimental Methods: A total of 24 male Hartley guinea pigs were apportioned randomly and equally into three groups: the control group (n=8), the high-fat diet group (n=8), and the capsicum diet group (n=8). After 12 weeks of modeling, samples were collected from the abdominal aorta serum, liver, gallbladder, stomach, and colon. Biochemical analysis for the serum total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein cholesterol. Inflammatory markers in the serum, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining (H-E) was used to observe morphological changes in the liver, gallbladder, stomach, and colon tissues. Compared with the normal control group, both high-fat and capsicum diets significantly elevated blood lipid levels and inflammatory indexes in the serum of guinea pigs (P\u0026lt;0.01), with the effects being more pronounced in the high-fat diet group (P\u0026lt;0.001). Pathological results indicated that both high-fat and capsicum diets induce damage to the liver, stomach, gallbladder, and colon, with the high-fat diet showing particularly significant effects. Conclusion: Consuming high-fat and capsicum foods may induce damage to the digestive system, resulting in abnormal lipid metabolism.\u003c/p\u003e","manuscriptTitle":"Comparative Study on the Effects of High-Fat Diet and Capsicum Diet on the Digestive Organs of Guinea Pigs","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-27 11:52:52","doi":"10.21203/rs.3.rs-4886822/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-30T08:19:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-29T13:52:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-22T17:14:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56772006996580183555125051839477806034","date":"2024-09-19T18:20:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16458512066084265969054058098422647602","date":"2024-09-19T08:52:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-19T08:42:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-19T08:36:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-29T14:18:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-28T12:39:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-09T11:42:55+00:00","index":"","fulltext":""}],"status":"published","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}}],"origin":"","ownerIdentity":"bb477260-ea9c-4a49-b083-8c59ec45802a","owner":[],"postedDate":"September 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38030661,"name":"Health sciences/Gastroenterology/Gastrointestinal diseases/Nutrition disorders"},{"id":38030662,"name":"Health sciences/Medical research/Experimental models of disease"},{"id":38030663,"name":"Biological sciences/Physiology/Metabolism/Feeding behaviour/Obesity"},{"id":38030664,"name":"Biological sciences/Zoology/Animal physiology"},{"id":38030665,"name":"Health sciences/Pathogenesis/Infection"},{"id":38030666,"name":"Health sciences/Gastroenterology/Hepatology/Liver diseases/Liver fibrosis"}],"tags":[],"updatedAt":"2025-05-26T16:03:59+00:00","versionOfRecord":{"articleIdentity":"rs-4886822","link":"https://doi.org/10.1038/s41598-025-93583-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-05-23 15:58:19","publishedOnDateReadable":"May 23rd, 2025"},"versionCreatedAt":"2024-09-27 11:52:52","video":"","vorDoi":"10.1038/s41598-025-93583-4","vorDoiUrl":"https://doi.org/10.1038/s41598-025-93583-4","workflowStages":[]},"version":"v1","identity":"rs-4886822","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4886822","identity":"rs-4886822","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}