Modulation of PON-1 by acetate reverses hepatic dysmetabolism in experimentally induced PCOS
AbstractPolycystic ovarian syndrome (PCOS) is well documented as the leading cause of infertility globally, and its long-term complications include non-alcoholic fatty liver disease (NAFLD) which results in a cascade of events leading to liver cirrhosis as well as hepatic carcinoma. Paraoxonase-1 (PON-1) is an antiatherosclerotic component, which protects against hepatic injury. Short-chain fatty acids (SCFAs), particularly acetate, are synthesized by the gut microbiota and play a central role in metabolic regulation. The present study investigated the impact of acetate on PCOS-associated hepatic dysregulation and probable involvement of PON-1. Female Wistar rats (8-week-old) were assigned into groups: control (CTL), acetate (ACT), letrozole (LET), and LET + ACT. Induction of PCOS was by administration of letrozole (1 mg/kg) for 21 days. After PCOS was confirmed in the rats, acetate (200 mg/kg) was administered for a period of 6 weeks. PCOS animals were characterized with multiple ovarian cysts; excessive androgen; reduced insulin sensitivity; me tabolic hormone (leptin and adiponectin) dysregulation; dyslipidemia; hepatic lipid peroxidation; lipotoxicity; increased hepatic caspase-6, as well as proinflammatory markers (NF-kB/SDF-1); and decreased antioxidant defense (NrF2) and HIF-1α. These perturbations were accompanied by suppression of PON-1 level. Nevertheless, administration of acetate mitigated these hepatic metabolic/cellular alterations. The present results pro...
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research
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