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Figure 2. The mechanisms of action of FGF21. Schematic illustration summarizing the pleiotropic metabolic and anti-fibrotic effects of FGF21 across adipose tissue, liver, and the hepatic microenvironment. In adipocytes, FGF21 enhances insulin-independent glucose uptake through upregulation of GLUT1 transporters, contributing to improved systemic glycaemic control and insulin sensitivity. In hepatocytes, FGF21 suppresses de novo lipogenesis and cholesterol biosynthesis via inhibition of SREBP-1/2 signalling, while promoting fatty acid oxidation. Within the hepatic microenvironment, FGF21 attenuates inflammatory signalling by reducing pro-inflammatory cytokines, suppresses activation of HSCs, and increases breakdown of fibrosis by elevating serum levels of plasminogen activators. Collectively, these coordinated actions contribute to improved metabolic homeostasis and attenuation of liver inflammation and fibrosis in MASLD. FGF21: Fibroblast growth factor 21; GLUT1: glucose transporter 1; HSC: hepatic stellate cell; IL: interleukin; MASLD: metabolic dysfunction-associated steatotic liver disease; NF-κB: nuclear factor kappa B; SREBP: sterol regulatory element-binding protein; TGF: transforming growth factor; TNF: tumor necrosis factor; α-SMA: alpha-smooth muscle actin.