Olaniyi Kehinde S, Areloegbe Stephanie E, Ul Haq Shah Mohd Z
Cardio/Endo-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
Cardio/Endo-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
Steroids. 2025 Feb;214:109554. doi: 10.1016/j.steroids.2024.109554. Epub 2024 Dec 18.
Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction is unclear. Therefore, the present research was designed to investigate the impact of epigenetic regulator, particularly short chain fatty acids (SCFAs) on adipose-ovarian dysfunction in PCOS rat model.
Eight-weeks-old female Wistar rats were allotted into four groups of n = 5, namely control, sodium acetate (SACT), letrozole (LETZ), and LETZ + SACT. Letrozole (1 mg/kg; p.o.) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; p.o.) for 6 weeks.
Letrozole-induced PCOS rats were presented with androgen excess, insulin resistance/hyperinsulinemia, ovarian cystic follicles, increased levels of anti-Mullerian hormone, leptin, with a corresponding decrease in 17-β estradiol, and adiponectin. In addition, the LETZ group also showed dyslipidemia, decreased levels of adipose/ovarian sirtuin-1, adipose triglyceride, increased lipase activity as well as ovarian triglyceride, with corresponding increase in adipose/ovarian lipid peroxidation, caspase-6, TGF-β1, inflammatory response (TNF-α, NF-κB and MIF) and decreased GSH. Adipose/ovarian mitofusin 2 depletion was observed in LETZ group and this was accompanied by elevated HDAC2. Nevertheless, administration of acetate reversed these perturbations.
Overall, the present results suggest that acetate ameliorates adipose-ovarian metabolic and endocrine disruptions that accompany PCOS, and these beneficial effects of acetate are associated with reduction of HDAC2 levels and elevation of mitofusin 2/sirtuin-1.
除了卵巢功能障碍和不孕外，多囊卵巢综合征（PCOS）患者还存在一些全身紊乱，包括脂肪组织的功能紊乱，这可能会加重PCOS的内分泌代谢异常。表观遗传变化与包括PCOS在内的代谢相关疾病有关。然而，其在脂肪 - 卵巢功能障碍中的致病作用尚不清楚。因此，本研究旨在探讨表观遗传调节剂，特别是短链脂肪酸（SCFAs）对PCOS大鼠模型中脂肪 - 卵巢功能障碍的影响。
将8周龄雌性Wistar大鼠分为四组，每组n = 5，即对照组、醋酸钠（SACT）组、来曲唑（LETZ）组和LETZ + SACT组。每天口服来曲唑（1 mg/kg），持续21天以诱导PCOS。此后，每天给动物口服SACT（200 mg/kg），持续6周。
来曲唑诱导的PCOS大鼠出现雄激素过多、胰岛素抵抗/高胰岛素血症、卵巢囊性卵泡、抗苗勒管激素、瘦素水平升高，同时17-β雌二醇和脂联素相应降低。此外，LETZ组还表现出血脂异常、脂肪/卵巢沉默调节蛋白-1水平降低、脂肪甘油三酯减少、脂肪酶活性增加以及卵巢甘油三酯增加，同时脂肪/卵巢脂质过氧化、半胱天冬酶-6、转化生长因子-β1、炎症反应（肿瘤坏死因子-α、核因子-κB和巨噬细胞移动抑制因子）相应增加，谷胱甘肽减少。在LETZ组中观察到脂肪/卵巢线粒体融合蛋白2减少，同时组蛋白去乙酰化酶2升高。然而，给予醋酸盐可逆转这些紊乱。
总体而言，本研究结果表明，醋酸盐可改善PCOS伴随的脂肪 - 卵巢代谢和内分泌紊乱，醋酸盐的这些有益作用与组蛋白去乙酰化酶2水平降低和线粒体融合蛋白2/沉默调节蛋白-1升高有关。
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