Metformin and Adipose Tissue: A Multifaceted Regulator in Metabolism, Inflammation, and Regeneration

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.