Feng Xueping, Xiao Juan, Wang Decai, Fu Xianzhao, Gao Jie, Jiang Minli, Li Jin, Jiang Lihe, Liang Xingwei, Huang Yanna, Jiang Qinyang
School of Basic Medicine, Youjiang Medical University for Nationalities, Baise, China.
College of Animal Science and Technology, Guangxi University, Nanning, China.
Front Endocrinol (Lausanne). 2025 Jul 9;16:1604302. doi: 10.3389/fendo.2025.1604302. eCollection 2025.
Butyric acid deficiency is implicated in polycystic ovary syndrome (PCOS), as evidenced by reduced levels in both clinical and preclinical models. Sodium butyrate (NaBu),a butyric acid substitute, has demonstrated therapeutic potential through gut-brain axis modulation, anti-inflammatory effects, and reproductive function protection. This study investigates NaBu's mechanistic role in PCOS pathophysiology.
PCOS rats received lipo-coated NaBu diet for three weeks. Systemic and tissue analyses included: serum hormone profiling, lipid metabolism assessment, ovarian/colonic histopathology, Short-chain fatty acids (SCFAs) analysis, and proteomics analysis. Primary granulosa cell cultures with lentiviral transfection elucidated molecular mechanisms. Reproductive performance was evaluated longitudinally.
Treatment with NaBu in PCOS rats resulted in reduced food intake, inhibited weight gain, improved abnormal lipid metabolism, restored estrus cycles and ovulation, lower serum levels of testosterone (T), insulin (INS), and luteinizing hormone (LH), and higher levels of estradiol (E) and progesterone (P). Additionally, NaBu treatment improved the morphology of polycystic ovaries, elevated colonic levels of G protein-coupled receptor 41 (GPR41), peptide tyrosine-tyrosine (PYY), and butyric acid, and enhanced reproductive performance in PCOS rats. Proteomic analysis and cell experiments suggested that upregulation of Cytochrome P450 1b1 (Cyp1b1) may play a crucial role in regulating E metabolism and P production, potentially contributing to the pathogenesis of PCOS and ovarian dysfunction.
These findings indicate that NaBu may exert its regulatory effects on appetite and hormone levels in the hypothalamus through the gut-brain-ovary axis, modulating the expression of ovarian steroidogenic factors, thereby improving follicular development and granulosa cell function, and enhancing reproductive performance.
丁酸缺乏与多囊卵巢综合征（PCOS）有关，临床和临床前模型中的水平降低证明了这一点。丁酸钠（NaBu）作为一种丁酸替代物，已通过肠-脑轴调节、抗炎作用和生殖功能保护显示出治疗潜力。本研究调查了NaBu在PCOS病理生理学中的作用机制。
PCOS大鼠接受脂质包被的NaBu饮食三周。全身和组织分析包括：血清激素谱分析、脂质代谢评估、卵巢/结肠组织病理学、短链脂肪酸（SCFAs）分析和蛋白质组学分析。用慢病毒转染的原代颗粒细胞培养阐明分子机制。纵向评估生殖性能。
PCOS大鼠用NaBu治疗后，食物摄入量减少，体重增加受到抑制，异常脂质代谢得到改善，发情周期和排卵恢复，血清睾酮（T）、胰岛素（INS）和促黄体生成素（LH）水平降低，雌二醇（E）和孕酮（P）水平升高。此外，NaBu治疗改善了多囊卵巢的形态，提高了结肠中G蛋白偶联受体41（GPR41）、肽YY（PYY）和丁酸的水平，并增强了PCOS大鼠的生殖性能。蛋白质组学分析和细胞实验表明，细胞色素P450 1b1（Cyp1b1）的上调可能在调节E代谢和P产生中起关键作用，可能导致PCOS和卵巢功能障碍的发病机制。
这些发现表明，NaBu可能通过肠-脑-卵巢轴对下丘脑的食欲和激素水平发挥调节作用，调节卵巢类固醇生成因子的表达，从而改善卵泡发育和颗粒细胞功能，并增强生殖性能。
