ENPP1 Is Correlated With Insulin Resistance and Lipid Molecules in PCOS Rats

Abstract BackgroundPrevious 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 ovarian syndrome (PCOS). This study aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS.MethodsEighteen 23-day-old Sprague-Dawley rats were divided into the PCOS and control groups (n= 9/group). Serum, ovaries, skeletal muscle, and subcutaneous and visceral fat were collected after 20 days. Pathological examination, immunofluorescence and western blotting analyses were performed. Serum indicator levels were measured, including ENPP1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), monocyte chemoattractant protein-1 (MCP-1), fasting blood glucose (FBG), fasting insulin (FINS), free fatty acids (FFAs), adiponectin (ADP), leptin, and serum lipids. ResultsThe levels of ENPP1, T, MCP-1, FBG, FINS, homeostasis model assessment of IR (HOMA-IR), FFAs, leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the PCOS group, while ADP and high-density lipoprotein cholesterol (HDL-C) were significantly lower than in the control group. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, MCP-1, HOMA-IR, FFAs, leptin, serum lipids and ADP. The 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. ConclusionENPP1 is highly associated with IR and lipid metabolism-related molecules, which may promote pathophysiological changes in PCOS.