Acetate abates adipose-ovarian endocrinometabolic disturbance in experimentally induced polycystic ovarian syndrome

Abstract

Background: Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction is unclear. Therefore, the present research was designed to investigate the impact of epigenetic regulator, particularly short chain fatty acids (SCFAs) on adipose-ovarian dysfunction in PCOS rat model.

Materials and methods: Eight-weeks-old female Wistar rats were allotted into four groups of n = 5, namely control, sodium acetate (SACT), letrozole (LETZ), and LETZ + SACT. Letrozole (1 mg/kg; p.o.) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; p.o.) for 6 weeks.

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-β 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-β1, inflammatory response (TNF-α, NF-κB and MIF) and decreased GSH. Adipose/ovarian mitofusin 2 depletion was observed in LETZ group and this was accompanied by elevated HDAC2. Nevertheless, administration of acetate reversed these perturbations.

Conclusion: Overall, the present results suggest that acetate ameliorates adipose-ovarian metabolic and endocrine disruptions that accompany PCOS, and these beneficial effects of acetate are associated with reduction of HDAC2 levels and elevation of mitofusin 2/sirtuin-1.

Keywords: Adipose; HDAC2; Inflammation; Mitochondrion; Ovary; PCOS.