PPARalpha is a key regulator of hepatic FGF21.
The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARalpha). Fasting or treatment of mice with the PPARalpha agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARalpha deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARalpha levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARalpha for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARalpha response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARalpha in humans will be of great interest.
Lundåsen
Thomas
T
Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine, M63, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Hunt
Mary C
MC
Nilsson
Lisa-Mari
LM
Sanyal
Sabyasachi
S
Angelin
Bo
B
Alexson
Stefan E H
SE
Rudling
Mats
M
D000818:Animals; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D047493:PPAR alpha; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors