FGF21 is an Akt-regulated myokine.

Fibroblast growth factor-21 (FGF21) functions as a metabolic regulator. The FGF21 transcript is reported to be abundantly expressed in liver, but little is known about the regulation of FGF21 expression in other tissues. In this study, we show that levels of FGF21 protein expression were similar in skeletal muscle and liver from fasted mice. FGF21 transcript and protein expression were upregulated in gastrocnemius muscle of skeletal muscle-specific Akt1 transgenic mice. Serum concentration of FGF21 was also increased by Akt1 transgene activation. In cultured skeletal muscle cells, FGF21 expression and secretion was regulated by insulin, Akt transduction and LY294002. These data indicate that skeletal muscle is a source of FGF21 and that its expression is regulated by a phosphatidylinosistol 3-kinase (PI3-kinase)/Akt1 signaling pathway-dependent mechanism.