@article{6251a879987341d4b2d6f371e9b5f2ed,
title = "Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21",
abstract = "Peroxisome proliferator-activated receptor α (PPARα) 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 PPARα. FGF21 is induced directly by PPARα in liver in response to fasting and PPARα 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 PPARα-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.",
keywords = "HUMDISEASE",
author = "Takeshi Inagaki and Paul Dutchak and Guixiang Zhao and Xunshan Ding and Laurent Gautron and Vinay Parameswara and Yong Li and Regina Goetz and Moosa Mohammadi and Victoria Esser and Elmquist, {Joel K} and Gerard, {Robert D.} and Burgess, {Shawn C} and Hammer, {Robert E} and Mangelsdorf, {David J} and Kliewer, {Steven A}",
note = "Funding Information: We thank L. Peng for technical assistance; N. Anderson and J. Horton for microarray analysis; J. Richardson, J. Shelton, and the UTSW Molecular Pathology Core Laboratory for histology and analysis; J. Repa for reagents and assistance during the early stages of this work; the UTSW Transgenic Core Facility; T. Willson (GlaxoSmithKline) for GW7647; and S. Strom (University of Pittsburgh) and the Liver Tissue Procurement and Distribution System (NIH grant DK92310) for human hepatocytes. We also thank E. Maratos-Flier and J. Flier for sharing unpublished data. This work was funded by NIH grants DK067158 (S.A.K.), P20RR20691 (S.A.K. and D.J.M.), U19DK62434 (D.J.M.), DK53301 (J.K.E.), U24DK076169 (S.C.B.), and DE13686 (M.M.); the Robert A. Welch Foundation (S.A.K. and D.J.M.); the Betty Van Andel Foundation (Y.L.); the Smith Family Foundation Pinnacle Program Project Award from the American Diabetes Association (J.K.E.); and the Howard Hughes Medical Institute (X.D. and D.J.M.). D.J.M. is an investigator of the Howard Hughes Medical Institute. ",
year = "2007",
month = jun,
day = "6",
doi = "10.1016/j.cmet.2007.05.003",
language = "English (US)",
volume = "5",
pages = "415--425",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}