SFEBES2023 Poster Presentations Metabolism, Obesity and Diabetes (70 abstracts)
Afe Babalola University, Ado-Ekiti, Nigeria
The complications of endocrine-metabolic disorders among women of reproductive age, such as polycystic ovarian syndrome (PCOS), are cascade of events leading to cardiovascular diseases, as well as non-alcoholic fatty liver disease (NAFLD) which is the leading cause of liver cirrhosis and hepatic carcinoma that often necessitates organ transplant. Paraoxonase-1 (PON-1) has been shown to be protective against metabolic assaults. However, its role in hepatic glucolipid regulation particularly in PCOS model has not been documented. Short-chain fatty acid (SCFAs) particularly butyrate, are essential modulators of metabolic health. The present study hypothesizes that butyrate would ameliorate hepatic dysmetabolism by upregulation of PON-1. Female Wistar rats (8-week-old) were allotted into groups; control (CONT), butyrate (BUTY), letrozole (PCOS), and PCOS+BUTY. Letrozole (1 mg/kg) was used to induce PCOS for 21 days. After confirmation of PCOS, butyrate (200 mg/kg) was administered for 6 weeks. Rats with PCOS showed multiple ovarian cysts, hyperandrogenism, reduced insulin sensitivity, hyperleptinemia, hypoadiponectinemia, dyslipidemia, and hepatic lipid peroxidation, lipotoxicity, as well as increased hepatic caspase-6, proinflammatory markers (NF-kB, SDF-1), and decreased antioxidant defense/sirtuine-1(NrF2), and HIF-1α with corresponding expression of inflammasome as evaluated immunohistochemically. These alterations were accompanied by suppressed level of PON-1. However, administration of butyrate attenuated these hepatic metabolic/cellular perturbations. The results of the present study demonstrate that butyrate mitigates hepatic glucolipid dysregulation and its attendant oxidative/inflammation in PCOS model through upregulation of PON-1 expression.