P058 ADIPOSE-OVARIAN CROSSTALK IN PCOS-INDUCED CARDIOMETABOLIC SYNDROME: THE ROLE OF HISTONE DEACETYLASE-2

Background and objective: In addition to ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality and subsequent cardiometabolic morbidities in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction and consequent cardiac events is under elucidation. Therefore, the present research was designed to investigate the role of epigenetic regulator, particularly histone deacetylase-2 on adipose-ovarian dysfunction and its attendant cardiometabolic syndrome in PCOS rat model. Methods: Eight-weeks-old nulliparous Wistar rats were allotted into four groups of n=5, namely control, acetate (SACT), letrozole (LETZ), and LETZ +SACT. Polycystic ovarian syndrome was induced with 1 mg/kg (p.o.) of LETZ for 21 days. Thereafter, the animals were treated with SACT (200 mg/kg; p.o.) for 6 weeks. Biochemical, histological and immunohistochemical evaluations were performed with appropriate methods. Results: Letrozole-induced PCOS rats were presented with androgen excess, insulin resistance/hyperinsulinemia, ovarian cystic follicles, increased levels of anti-Mullerian hormone, leptin, with a corresponding decrease in 17-Beta estradiol, and adiponectin. In addition, the LETZ group also showed dyslipidemia, decreased levels of adipose/ovarian sirtuin-1, adipose triglyceride, increased lipase activity as well as ovarian triglyceride, with corresponding increase in adipose/ovarian lipid peroxidation, caspase-6, TGF-Beta1, inflammatory response (TNF-alpha, NF-kappaB and MIF) and decreased GSH. Adipose/ovarian mitochondrial dysfunction with evidence of decreased MATPS/Mfn2 were observed in LETZ group. The cardiac tissue of PCOS animals also revealed inflammasome and oxidative stress and altogether were accompanied by elevated expression of HDAC2. Nevertheless, administration of acetate reversed these perturbations. Conclusion: Overall, the present results suggest that acetate ameliorates adipose-ovarian dysfunction and cardiometabolic pathology that accompany PCOS by suppression of HDAC2. The present data possibly provides a clinical relevance for the management of cardiometabolic syndrome in PCOS individuals.