1. Acetate attenuates hypothalamic pyroptosis in experimentally induced polycystic ovarian syndrome.
- Author
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Olaniyi KS, Agan SU, Areloegbe SE, Sabinari IW, Oniyide AA, Enye LA, Omoaghe AO, Adekeye AO, and Adeoluwa OA
- Subjects
- Female, Animals, Rats, Insulin Resistance, NF-E2-Related Factor 2 metabolism, Disease Models, Animal, Letrozole pharmacology, Triglycerides blood, Triglycerides metabolism, Luteinizing Hormone blood, Follicle Stimulating Hormone blood, Adiponectin metabolism, Adiponectin blood, Testosterone blood, Leptin blood, Leptin metabolism, Gonadotropin-Releasing Hormone metabolism, gamma-Aminobutyric Acid metabolism, Polycystic Ovary Syndrome chemically induced, Polycystic Ovary Syndrome metabolism, Polycystic Ovary Syndrome drug therapy, Polycystic Ovary Syndrome pathology, Hypothalamus metabolism, Hypothalamus drug effects, Hypothalamus pathology, Pyroptosis drug effects, Rats, Wistar, Hypoxia-Inducible Factor 1, alpha Subunit metabolism
- Abstract
This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed 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. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α., (© 2024. The Author(s).)
- Published
- 2024
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