Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21.

TitleEndocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21.
Publication TypeJournal Article
Year of Publication2007
AuteursInagaki, T, Dutchak, P, Zhao, G, Ding, X, Gautron, L, Parameswara, V, Li, Y, Goetz, R, Mohammadi, M, Esser, V, Elmquist, JK, Gerard, RD, Burgess, SC, Hammer, RE, Mangelsdorf, DJ, Kliewer, SA
JournalCell Metab
Volume5
Issue6
Pagination415-25
Date Published2007 Jun
ISSN1932-7420
KeywordsAdenoviridae, Adipose Tissue, Animals, Cells, Cultured, Chromatin Immunoprecipitation, Fasting, Female, Fibroblast Growth Factors, Hepatocytes, Humans, Immunoblotting, Lipolysis, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Plasmids, PPAR alpha, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction, Transfection
Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the utilization of fat as an energy source during starvation and is the molecular target for the fibrate dyslipidemia drugs. Here, we identify the endocrine hormone fibroblast growth factor 21 (FGF21) as a mediator of the pleiotropic actions of PPARalpha. FGF21 is induced directly by PPARalpha in liver in response to fasting and PPARalpha agonists. FGF21 in turn stimulates lipolysis in white adipose tissue and ketogenesis in liver. FGF21 also reduces physical activity and promotes torpor, a short-term hibernation-like state of regulated hypothermia that conserves energy. These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.

DOI10.1016/j.cmet.2007.05.003
Alternate JournalCell Metab.
PubMed ID17550777
Grant ListDE13686 / DE / NIDCR NIH HHS / United States
DK067158 / DK / NIDDK NIH HHS / United States
DK53301 / DK / NIDDK NIH HHS / United States
P20RR20691 / RR / NCRR NIH HHS / United States
U19DK62434 / DK / NIDDK NIH HHS / United States
U24DK076169 / DK / NIDDK NIH HHS / United States
/ / Howard Hughes Medical Institute / United States