Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO(2)max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.