FGF21

FGF21, fibroblast growth factor 21, alias FGF-21, is a stress-inducible hormone produced by the liver and other metabolically active tissues, and is a new member of the fibroblast growth factor family.FGF21 exerts its biological effects by binding to fibroblast growth factor receptors (FGFRs) 1c, 2c, and 3c, and requires β-Klotho as a cofactor to activate multiple intracellular signaling pathways to exert its biological effects. Its main roles include promoting fatty acid oxidation, regulating energy expenditure, increasing glucose uptake, promoting adipocytokine secretion, and regulating lipid metabolism.

FGF21 has a wide range of biological significance, and plays a role in attenuating hepatic stress, protecting hepatocytes, inhibiting apoptosis and inflammatory signaling, and inhibiting the differentiation of hepatic stellate cells into collagen-secreting myofibroblasts.FGF21 also interacts with other hormones such as insulin, glucagon, and thyroid hormones to regulate systemic and hepatic metabolism. In addition, agonists of FGF21 have shown potential in the treatment of metabolic dysfunction-associated steatohepatitis (MASH) to improve metabolic function and lipid metabolism, and to reduce hepatic fat content and improve hepatic histologic features in preclinical models.Agonists of FGF21, such as efruxifermin and pegozafermin, are under development and have been studied in multiple metabolic disease indications, including obesity, hypertriglyceridemia, dyslipidemia, type 2 diabetes mellitus, and metabolic dysfunction-related fatty liver disease/metabolic dysfunction-related steatohepatitis .