Wei Xin-Li, Tao Ming-Hao, Li Run-Hao, Ge Shi-Hui, Xiao Wei
The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, China.
State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Lianyungang, China.
Endocrinol Metab (Seoul). 2025 Aug;40(4):523-538. doi: 10.3803/EnM.2025.2371. Epub 2025 Aug 8.
Metformin, a first-line treatment for type 2 diabetes mellitus (T2DM), has garnered attention due to its pleiotropic effects beyond glycemic control. In addition to improving insulin sensitivity and inhibiting hepatic gluconeogenesis, metformin modulates inflammation, oxidative stress, and cellular metabolism, particularly within adipose tissue. Adipose tissue is a crucial endocrine organ that plays a central role in metabolic homeostasis and is integral to obesity and T2DM pathogenesis. This review discusses the actions of metformin on white and brown adipose tissues, extracellular matrix remodeling, mature adipocytes, and adipose-derived stem cells. Through both AMP-activated protein kinase-dependent and independent pathways, metformin influences adipogenesis, lipolysis, adipokine secretion, fibrosis, and cellular senescence. We also focus on how the drug concentration influences its biological effects, emphasizing the necessity of physiologically relevant experimental models. These insights deepen our understanding of metformin's therapeutic potential in metabolic and age-related disorders.
二甲双胍作为2型糖尿病（T2DM）的一线治疗药物，因其在血糖控制之外的多效性作用而受到关注。除了提高胰岛素敏感性和抑制肝糖异生外，二甲双胍还能调节炎症、氧化应激和细胞代谢，特别是在脂肪组织中。脂肪组织是一个关键的内分泌器官，在代谢稳态中起核心作用，并且是肥胖和T2DM发病机制所不可或缺的。本综述讨论了二甲双胍对白色和棕色脂肪组织、细胞外基质重塑、成熟脂肪细胞和脂肪来源干细胞的作用。通过AMP激活的蛋白激酶依赖性和非依赖性途径，二甲双胍影响脂肪生成、脂肪分解、脂肪因子分泌、纤维化和细胞衰老。我们还关注药物浓度如何影响其生物学效应，强调生理相关实验模型的必要性。这些见解加深了我们对二甲双胍在代谢和年龄相关疾病中的治疗潜力的理解。
