FGF21

FGF21 (fibroblast growth factor 21) is an endocrine member of the FGF19 subfamily that functions as a systemic metabolic hormone regulating energy balance, glucose homeostasis, and lipid metabolism through fibroblast growth factor receptor (FGFR) signaling pathways.^[1][2] Mechanistically, FGF21 signals through a receptor complex composed of FGFR1 and β-Klotho (KLB), and β-Klotho is required for efficient activation of specific FGFR isoforms by FGF21.^[3][4][5] Activation of the FGF21-FGFR1/β-Klotho axis enhances insulin sensitivity, promotes energy expenditure, regulates lipid utilization, and coordinates metabolic communication among liver, adipose tissue, and other metabolic organs.^[2][6][7] In metabolic disease models, FGF21 improves glucose and lipid handling, stimulates hepatic fatty acid oxidation, reduces hepatic lipid accumulation, and is closely linked to obesity, type 2 diabetes, and fatty liver disease.^[8][9][10] Compared with related endocrine FGFs, FGF21 is distinguished from FGF23, which utilizes α-Klotho-dependent signaling, whereas FGF21 preferentially activates β-Klotho-associated receptor complexes and primarily regulates systemic metabolic homeostasis.^[4][5][3] FGF21 also differs functionally from FGF19, although both hormones require β-Klotho for receptor engagement and participate in endocrine metabolic regulation.^[11][12] For experimental applications, recombinant FGF21 proteins, FGF21 analogs, and β-Klotho-targeting agonists are widely used to investigate metabolic signaling mechanisms and therapeutic responses in obesity, diabetes, and nonalcoholic fatty liver disease models.^[11][13][14]