Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease

Metabolic dysfunction-associated fatty liver disease (MAFLD) poses a significant challenge in modern medicine due to its high prevalence. The pathogenesis of MAFLD involves a complex dysmetabolic process consistent with the "multiple-hit" hypothesis. This process includes excessive triglyceride (TC) accumulation within hepatocytes, lipotoxicity, insulin resistance (IR), chronic low-grade inflammation, and increased oxidative stress. The role of leptin in the liver has been extensively studied, demonstrating both direct effects on hepatic cells and indirect actions mediated through the central nervous system (CNS). In MAFLD, leptin modulates several physiological processes: it improves glucose metabolism by enhancing insulin sensitivity and lowering glucose levels; regulates lipid metabolism by promoting β-oxidation and TC export while inhibiting lipogenesis; and contributes to fibrogenesis by upregulating transforming growth factor-β (TGF-β) expression and activating hepatic stellate cells (HSCs) and the immune response. This review explores the structure of leptin, its primary physiological functions, its potential role in MAFLD pathogenesis, and its promise as a novel therapeutic target.