Ectonucleotide Pyrophosphatase Phosphodiesterase 1 Is Correlated With Insulin Resistance and Lipid Metabolism Disorders in the Rat Model of Polycystic Ovary Syndrome

Jing Xia, Yi‐Qing Yang, Zhe Yang, Gengxiang Wu, Jing Yang
In: Research Square · 2022 · doi:10.21203/rs.3.rs-1208513/v1 · W4205959103
preprint OA: green CC0
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is elevated in PCOS rats and correlates with insulin resistance and dyslipidemia, suggesting a role in PCOS pathophysiology.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

This preprint investigated the expression and associations of ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) across multiple tissues in a dehydroepiandrosterone (DHEA)-induced rat model of polycystic ovary syndrome (PCOS), using 18 Sprague-Dawley rats (n=9/group) with pathological assessment, immunofluorescence, qRT-PCR, western blotting (ovaries), and serum measurements (ENPP1, hormones, fasting glucose/insulin, lipids). ENPP1 levels were higher in the ovaries at the protein level, and circulating ENPP1 was significantly elevated in PCOS rats alongside increased testosterone, fasting blood glucose, HOMA-IR, free fatty acids, and lipid measures, while adiponectin and HDL-C were lower. Spearman correlations showed ENPP1 was associated with multiple insulin resistance and lipid-related molecules, and ENPP1 mRNA was increased in ovaries, skeletal muscle, subcutaneous fat, and visceral fat, alongside BAX and IRS1 mRNA changes. A major caveat is that the findings are from a small animal model and the manuscript is not peer reviewed. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Previous studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovary syndrome (PCOS). This study was aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS. Eighteen 23-day-old Sprague-Dawley rats were divided into PCOS and control groups (n= 9/group). Samples were collected after 20 days. Pathological examination and immunofluorescence were performed. Western blotting results of ENPP1 in the ovaries were analysed. Serum levels of ENPP1, hormones, fasting blood glucose (FBG), serum lipids were measured. Levels of ENPP1, testosterone (T), FBG, fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), free fatty acids (FFAs), leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in PCOS group, while adiponectin (ADP) and high-density lipoprotein cholesterol (HDL-C) were significantly lower. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, HOMA-IR, FFAs, leptin, serum lipids and ADP. MRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. Our results revealed that ENPP1 is highly associated with IR and lipid metabolism-related molecules, which may have play important roles in PCOS pathophysiological changes.

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