New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis

Abstract

Metformin, a widely used antidiabetic drug, modulates the cellular physiology and metabolism of various body tissues, including adipose tissue. Adipogenesis, a complex process in which mesenchymal stem cells (MSC) differentiate into functional adipocytes, plays a key role in metabolic health and represents a potential therapeutic target for diverse metabolic disorders. Notably, recent evidence suggests that metformin modulates adipocyte differentiation. This narrative review explores the effects of metformin on cellular metabolism, with a particular focus on adipogenesis. The findings compiled in this review show that metformin regulates glucose and lipid metabolism in multiple tissues, including skeletal muscle, adipose tissue, liver, and intestine. Furthermore, metformin modulates adipogenesis through AMP-activated protein kinase (AMPK)-dependent and independent mechanisms in 3T3-L1 cells and adipose-derived stem cells. The review also emphasizes that metformin can promote or inhibit adipogenesis and lipid accumulation, depending on its concentration. Additionally, metformin attenuates inflammatory pathways by reducing the production of proinflammatory cytokines such as IL-6, MCP-1, and COX-2. Finally, evidence supports that vitamin D enhances the anti-inflammatory actions of metformin and promotes cell differentiation toward a beige adipocyte phenotype. In summary, this review examines the molecular actions of metformin to propose potential new therapeutic strategies for managing obesity and related metabolic diseases.