TMT-Based Proteomics Analysis of the Intervention Effect of Orlistat on Polycystic Ovary Syndrome Rats Induced by Letrozole Combined with a High-Fat Diet

[Image: see text] Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine and metabolic disease. Orlistat as a lipase inhibitor may improve the pathological characteristics of PCOS and is the sole antiobesity agent available in various countries. In this study, the PCOS rat models were established using letrozole and high-fat diet. Tandem Mass Tag labeling peptide coupled with liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach was employed to investigate the differentially expressed ovarian proteins (DEPs) in the PCOS and control rats for the effect of PCOS, and in the PCOS and orlistat-treated PCOS rats for the effect of orlistat in PCOS. The orlistat attenuated the body weight gain; decreased the levels of testosterone, luteinizing hormone, a ratio of luteinizing/follicle-stimulating hormones; increased the level of estradiol; and recovered the estrous cycle in PCOS rats. In addition, 795 and 119 DEPs were found in PCOS and orlistat-treated PCOS groups, respectively. Based on the Gene Ontology and Kyoto Encyclopedia of Gene and Genomes pathway analysis of DEPs, orlistat restored the disturbed metabolism of linoleic acid, arachidonic acid, galactose, and glycerolipids, and then improved the chronic inflammation in PCOS rats. This study analyzed the ovarian proteome of orlistat-treated PCOS rats and identified targeted proteins, which explored the pathogenesis of PCOS and the potential effects of orlistat in PCOS rats.