Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 29;8(28):24831-24840.
doi: 10.1021/acsomega.3c00578. eCollection 2023 Jul 18.

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  1   2   3 , Enli Wang  2 , Wenbin Chen  4 , Baihui Xu  2 , Chen Chen  5 , Guimin Zhang  6 , Jingchun Yao  2
Affiliations

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 et al. ACS Omega. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Effect of orlistat treatment on body weight and serum sex hormone levels in letrozole-induced PCOS rats. (A) Changes in body weight of rats in each group (0–2 weeks was the adaptation period, 2–6 weeks was the letrozole-induced PCOS rat period, and 6–14 weeks was the orlistat treatment period). (B) T, (C) LH, (D) FSH, (E) LH/FSH, (F) E2. All values represent mean ± SD (n = 10/group). *p < 0.05, **p < 0.01 vs CON; #p < 0.05, ##p < 0.01 vs PCOS. CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS; T: testosterone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; E2: estradiol.
Figure 2
Figure 2
(A–C) Changes of estrous cycle of rats in CON, PCOS, and ORL-PCOS groups. (D–G) Relative time span of each stage of the cycle. P: proestrus; E: estrus; M: metestrus; D: diestrus; CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS.
Figure 3
Figure 3
(A) Volcano plot of proteins identified from PCOS vs CON group. (B) Volcano plot of proteins identified from ORL-PCOS vs PCOS group. The volcano plot was mapped on the basis of the fold change and p values. Red and blue dots: DEPs; gray dots: proteins without difference; DEPs: differentially expressed proteins; CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS.
Figure 4
Figure 4
Enriched GO terms of the DEPs. (A) GO enrichment of the DEPs in PCOS vs CON group. (B) GO enrichment of the DEPs in ORL-PCOS vs PCOS group. GO: Gene Ontology; DEPs: differentially expressed proteins; CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS; CC: cellular component; MF: molecular function; BP: biological process.
Figure 5
Figure 5
Enriched KEGG pathway analysis of the DEPs. (A) KEGG pathway analysis of the DEPs in PCOS vs CON group. (B) KEGG pathway analysis of the DEPs in ORL-PCOS vs PCOS group. KEGG: Kyoto Encyclopedia of Gene and Genomes; DEPs: differentially expressed proteins; CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS.
Figure 6
Figure 6
Protein–protein interaction (PPI) network based on DEPs. (A) PCOS vs CON group. (B) ORL-PCOS vs PCOS group. DEPs: differentially expressed proteins; CON: control; PCOS: polycystic ovary syndrome; ORL-PCOS: orlistat-treated PCOS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Azziz R.; Carmina E.; Chen Z.; Dunaif A.; Laven J. S.; Legro R. S.; Lizneva D.; Natterson-Horowtiz B.; Teede H. J.; Yildiz B. O. Polycystic ovary syndrome. Nat. Rev. Dis. Primers 2016, 2, 16057.10.1038/nrdp.2016.57. - DOI - PubMed
    1. Teede H. J.; Misso M. L.; Costello M. F.; Dokras A.; Laven J.; Moran L.; Piltonen T.; Norman R. J.; et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum. Reprod. 2018, 33, 1602–1618. 10.1093/humrep/dey256. - DOI - PMC - PubMed
    2. Wild R. A. Long-term health consequences of PCOS. Hum. Reprod. Update 2002, 8, 231–241. 10.1093/humupd/8.3.231. - DOI - PubMed
    1. Wang W.; Jiang Q.; Niu Y.; Ding Q.; Yang X.; Zheng Y.; Hao J.; Wei D. Proteomics and bioinformatics analysis of follicular fluid from patients with polycystic ovary syndrome. Front. Mol. Biosci. 2022, 9, 95640610.3389/fmolb.2022.956406. - DOI - PMC - PubMed
    1. Zhang Z.; Wu S.; Stenoien D. L.; Pasa-Tolic L. High-throughput proteomics. Annu. Rev. Anal. Chem. 2014, 7, 427–454. 10.1146/annurev-anchem-071213-020216. - DOI - PubMed
    1. Sim Y. J.; Ryu A. R.; Lee M. Y. Proteomic analysis of human follicular fluid from polycystic ovary syndrome patients. Biotechnol. Appl. Biochem. 2022, 69, 289–295. 10.1002/bab.2108. - DOI - PubMed