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

Jianmei Yang; Enli Wang; Wenbin Chen; Baihui Xu; Chen Chen; Guimin Zhang; Jingchun Yao

doi:10.1021/acsomega.3c00578

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

ACS Omega. 2023 Jun 29;8(28):24831-24840. doi: 10.1021/acsomega.3c00578. eCollection 2023 Jul 18.

Authors

Jianmei Yang^{1

2

3}, Enli Wang², Wenbin Chen⁴, Baihui Xu², Chen Chen⁵, Guimin Zhang⁶, Jingchun Yao²

Affiliations

¹ Department of Pediatric Endocrinology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
² State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi 276006, Shandong, China.
³ Department of Pediatric Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China.
⁴ Scientific Center, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
⁵ Endocrinology, SBMS, Faculty of Medicine, The University of Queensland, St Lucia, QLD 4072, Australia.
⁶ National Engineering and Technology Research Center of Chirality Pharmaceutical, Lunan Pharmaceutical Group Co. Ltd., Linyi 276006, Shandong, China.

Abstract

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.