These findings suggest that the elevation of BTG2 by gluconeogenic signals modulates hepatic FGF21 homeostasis by inducing the expression of Klf15. Therefore, as depicted in Fig. 6, a molecular mechanism involving hepatic FGF21 homeostasis in response to BTG2-KLF15 signaling may provide the basis for the development of novel therapeutic agents for the treatment of metabolic disorders. This evidence concerns the gene BTG2 and metabolic disease.