Endocrine Abstracts

Background of Study: Polycystic ovarian syndrome (PCOS) is an endocrine disorder, contributing to increased neurodegenerative disorders including hypothalamic disturbance. Short chain fatty acid (SCFA) has been reported to regulate metabolic health. However, its therapeutic nature in hypothalamic dysfunction, especially in PCOS individuals is unknown. This study hypothesized that SCFA reverses hypothalamic injury and its related abnormalities in experimentally induced PCOS rat model, possibly by modulating GABA.

Materials and Methods: Eight week old female Wister rats were divided into four groups (n=5), namely control, PCOS, acetate-treated and PCOS+acetate-treated. PCOS was induced by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks.

Results: PCOS rats were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles, there was also a significant increase in plasma and hypothalamic triglyceride levels, triglyceride glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and hypothalamic caspase 6, plasma LH, an increase in plasma adiponectin, GnRH, FSH, and hypothalamic HIF-1α and NrF2 as well as severe apoptosis and inflammasome expression. These were accompanied by decreased level of GABA and the alterations were reversed when treated with SCFA, acetate.

Conclusion: Collectively, the present results suggests the therapeutic impact of SCFA on hypothalamic apoptosis and its related comorbidity in PCOS via modulation of GABA. The study therefore provides a clinical relevance in the management of hypothalamic disorder especially in PCOS individuals.

Keywords: Acetate; Apoptosis; GABA; Hypothalamus; Insulin resistance; PCOS.