Fibroblast growth factor 21 is required for alcohol‐induced adipose tissue lipoatrophy in mice

Abstract

Fibroblast growth factor 21 (FGF‐21) is a member of FGF superfamily and has been identified as a potent metabolic regulator. Studies have shown that FGF‐21 plays a critical role in adipose tissue lipolysis. FGF‐21 KO mice and controls (C57BL/6 mice) were fed Lieber deCarli liquid diet containing 5% alcohol or pair‐fed with isocaloric maltose dextrin for 12 days. Six hours before sacrificing, a binge dose of alcohol at 6g/kg body weight was given to the mice by gavage. Alcohol significantly increased serum and hepatic FGF‐21 in wild type mice. Alcohol decreased white adipose tissue mass in wild type mice, but not in FGF‐21 KO mice, indicating a requirement of FGF‐21 for alcohol‐induced adipose tissue lipoatrophy. A mechanism underlying adipose tissue lipolysis is the cAMP‐mediated hormone sensitive lipase (HSL) pathway, which is regulated by catecholamines, nicotinic acid, and insulin. Perilipin (PLIN) is a coating protein for lipid droplet and protects lipids waiting to be degraded. Alcohol increased phosphorylation of PLIN and HSL in wild type mice, which may be responsible for the observed adipose lipolysis by alcohol. Alcohol did not affect PLIN and HSL phosphorylation in FGF‐21 knockout mice. Our results suggest that FGF‐21 is a potential regulator of alcohol‐induced white adipose tissue hyperlipolysis via HSL/PLIN pathway, which may contribute to alcoholic fatty liver formation.