FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology
Figure 2
Mechanism of action and regulatory mechanism of the gene expression of FGF21. (a) Hepatic Fgf21 expression is induced by the activation of PPARα. NEFA binds to and activates PPARα. The ligand-bound PPARα forms a heterodimer with RXRs and induces the expression of Fgf21. The FGF21 inhibits lipolysis in adipocytes. In cultured adipocytes, FGF21 signaling is transduced by activating the βKlotho-FGFR1c complex. However, FGF21 signaling can be transduced in βKlotho knockout mice, indicating the existence of a βKlotho-independent FGF21 signaling pathway. The regulatory process forms a negative feedback loop in the control of lipolysis by FGF21. (b) Feeding with a ketogenic diet (KD) mimics the metabolic conditions of chronic starvation. KD induces hepatic Fgf21 expression and torpor. FGF21 attenuates torpor induced by KD.
