Circadian expression of FGF21 is induced by PPARalpha activation in the mouse liver.
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor that regulates the expression of genes associated with lipid metabolism. Recent studies have suggested that the expression of PPARalpha-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 PPARalpha, effectively induced FGF21 expression, whereas a daytime injection did not affect it. Furthermore, bezafibrate-induced circadian FGF21 expression was abolished in PPARalpha-deficient mice. These observations suggest that bezafibrate-induced circadian FGF21 expression is due to circadian variations in the responsiveness of the PPARalpha system in the liver.
Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. k-ooishi@aist.go.jp
Katsutaka
K
Oishi
Daisuke
D
Uchida
Norio
N
Ishida
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002940:Circadian Rhythm / Q000235:genetics*; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D000960:Hypolipidemic Agents; D047493:PPAR alpha; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D001629:Bezafibrate