Metformin Improves Palmitate-Induced Follicular Granulosa Cell Dysfunction by Activating ULK1-Mediated Autophagy

文献类型： 外文期刊

第一作者： Heng, Nuo

作者： Heng, Nuo;Wang, Feng;Heng, Nuo;Hao, Haisheng;Hu, Yingfan;Wang, Yi;Wang, Huan;He, Wei;Zhu, Ni;Wang, Rui;Xuan, Xiuli;Zhu, Huabin;Zhao, Shanjiang

作者机构：

关键词： Palmitic acid; Granulosa cells; Apoptosis; Autophagy; Mitochondria; Metformin

期刊名称：REPRODUCTIVE SCIENCES （ 影响因子：2.5； 五年影响因子：2.8 ）

ISSN： 1933-7191

年卷期： 2025 年 32 卷 7 期

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收录情况： SCI

摘要： Obesity has become a global epidemic with major implications for fertility. In particular, obesity can trigger follicular atresia by initiating the apoptosis of granulosa cells (GCs). Emerging evidence suggests that this process may be closely linked to the dysregulation of cellular autophagy. Metformin has been shown to restore autophagic flux and mitigate obesity-related cellular dysfunction in mice; however, the ability of metformin to alleviate lipid overload-induced damage in goat granulosa cells has yet to be investigated. Analyses showed that 400 mu M palmitic acid (PA) significantly increased lipid accumulation and reduced cell viability (P < 0.05) in goat granulosa cells. Furthermore, PA impaired mitochondrial function, associated with a significant increase in the populations of both early and late apoptotic cells (P < 0.05). However, treatment with 5 mu M metformin (MET) under PA exposure significantly enhanced the viability of GCs and reduced the expression levels of pro-apoptotic BAX (P < 0.05). Next, we evaluated the effect of MET on cellular autophagy and found that MET treatment significantly downregulated the expression levels of phosphorylated mTORC1 (Ser2448), LC3B, and P62 while upregulating the expression levels of ULK1 in PA-treated GCs (P < 0.05). Our findings indicate that metformin improved palmitate-induced granulosa cell dysfunction by activating ULK1-mediated autophagy. Our findings will advance our understanding of reproductive dysfunction in obese ruminants, and provide a theoretical foundation for improving fertility in obese mammals.

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