Circadian expression of FGF21 is induced by PPARα activation in the mouse liver

Peroxisome proliferator-activated receptor a (PPAR alpha) is a nuclear receptor that regulates the expression of genes associated with lipid metabolism. Recent studies have suggested that the expression of PPAR alpha-dependent fibroblast growth factor 21 (FGF21) plays important roles in adaptation to fasting, such as lipolysis and ketogenesis. We found that a nighttime injection of bezafibrate, a ligand of PPAR alpha, effectively induced FGF21 expression, whereas a daytime injection did not affect it. Furthermore, bezafibrate-induced circadian FGF21 expression was abolished in PPAR alpha-deficient mice. These observations suggest that bezafibrate-induced circadian FGF21 expression is due to circadian variations in the responsiveness of the PPAR alpha system in the liver. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.