Endocrine Abstracts

Impaired adipose tissue remodeling has been suggested as a pathophysiological driver of endocrinometabolic events in PCOS models, a condition that affects 6-21% of reproductive-aged women worldwide. Mitochondrial dysfunction, especially in the adipocyte plays a key role in adipose tissue inflammation that possibly aggravates endocrine/metabolic phenotypes in PCOS. Studies have reported Short-chain-fatty acids (SCFAs) as metabolic modulators that potentiate energy homeostasis. However, the impact of SCFAs, particularly butyrate, on mitochondrial dysfunction/inflammation in the adipocyte of PCOS individuals is unknown. The present study therefore hypothesized that butyrate would reverse adipose mitochondrial dysfunction/inflammation and endocrine/metabolic features in experimental PCOS rat model. Eight-week-old female Wistar rats were assigned into groups, n=5, namely control (CONT), sodium butyrate (SBUT), PCOS, and PCOS+SBUT. Polycystic ovarian syndrome (PCOS) was induced with Letrozole (1 mg/kg) for 21 days. After the confirmation of PCOS, the animals were treated with sodium butyrate (200 mg/kg) for six weeks uninterruptedly. The experimental PCOS animals expressed morphological alterations with multiple ovarian cysts and hormonal/metabolic changes characterized by hyperandrogenism, hypoestrogenism, elevated anti-Mullerian hormone and hyperinsulinemia/insulin resistance. In addition, animals also demonstrated decreased plasma triglyceride, adiponectin, and increased leptin, with corresponding decrease in adipose triglyceride, lipase, and increase in proinflammatory markers (NF-kB and TNF-α). A significant increase in adipose mitochondrial caspase-6, SDF-1, NF-kB, MDA, and decreased NrF2 and ATP synthase were also observed in experimental PCOS animals and these were immunohistochemically confirmed by severe expression of NLRP3 in the adipose tissue. These alterations were accompanied by altered adipose MIF and HIF-1α. Nevertheless, administration of butyrate alleviates these morphological, mitochondrial, biochemical, and immunohistochemical alterations in both ovary and adipose tissue of PCOS animals. The results suggest the ameliorative effect of SCFA, butyrate on adipose mitochondrial dysfunction and/or inflammation in PCOS by modulation of HIF-1α/MIF-dependent pathway.