Adipogenesis Under Leptin Control: Mechanisms and Model-Specific Effects

Adipogenesis is one way by which adipose tissue expands in our body. It is a complex tightly regulated process involving differentiation of mesenchymal stem cells (MSCs) into mature, lipid-containing adipocytes. One of the byproducts of this mechanism is leptin, an adipokine that plays a pivotal role in regulating food intake and energy homeostasis. While the increase in leptin secretion in proportion to fat mass expansion shows that leptin functions as a downstream marker of adipogenesis, emerging studies suggest that leptin itself may influence the adipogenesis process and act as a regulator. However, despite much research done to explore this, its role remains incompletely understood and often contradictory, with studies reporting pro-adipogenic, anti-adipogenic, or neutral effects depending on experimental context. These discrepancies highlight the influence of factors such as leptin concentration, timing of exposure, cell type, adipose depot, and species differences. This review gathers current evidence on leptin’s role in adipogenesis, integrating findings from diverse experimental models and biological systems. We further examine the underlying molecular mechanisms and signaling pathways involved, aiming to clarify the context-dependent effects of leptin and identify key knowledge gaps to guide future research in adipose tissue biology and metabolic disease.