@article{d18b6442ee304772bd2d285bfeb9a089,
title = "Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis",
abstract = "The liver and intestine play crucial roles in maintaining bile acid homeostasis. Here, we demonstrate that fibroblast growth factor 15 (FGF15) signals from intestine to liver to repress the gene encoding cholesterol 7α-hydroxylase (CYP7A1), which catalyzes the first and rate-limiting step in the classical bile acid synthetic pathway. FGF15 expression is stimulated in the small intestine by the nuclear bile acid receptor FXR and represses Cyp7a1 in liver through a mechanism that involves FGF receptor 4 (FGFR4) and the orphan nuclear receptor SHP. Mice lacking FGF15 have increased hepatic CYP7A1 mRNA and protein levels and corresponding increases in CYP7A1 enzyme activity and fecal bile acid excretion. These studies define FGF15 and FGFR4 as components of a gut-liver signaling pathway that synergizes with SHP to regulate bile acid synthesis.",
author = "Takeshi Inagaki and Mihwa Choi and Antonio Moschetta and Li Peng and Cummins, {Carolyn L.} and McDonald, {Jeffrey G.} and Guizhen Luo and Jones, {Stacey A.} and Bryan Goodwin and Richardson, {James A.} and Gerard, {Robert D.} and Repa, {Joyce J.} and Mangelsdorf, {David J.} and Kliewer, {Steven A.}",
note = "Funding Information: We thank Drs. Joe Goldstein and David Russell for critically reading the manuscript; Drs. David Russell, Wallace McKeehan, and Thomas Reh for the SHP −/− , FGFR4 −/− , and FGF15 −/− mice, respectively; Dr. David Russell for the CYP7A1 antisera; Patrick Maloney and Dr. Tim Willson for GW4064; and Drs. Jonathan Cohen and Stephen Turley for assistance in measuring CYP7A1 activity. This work was funded by National Institutes of Health grants DK067158 (S.A.K.) and U19DK62434 (S.A.K. and D.J.M.), the LIPID MAPS Large-Scale Collaborative Grant GM069338 (J.G.M.), the Robert A. Welch Foundation (S.A.K. and D.J.M.), and the Howard Hughes Medical Institute (A.M., C.L.C., and D.J.M.). D.J.M. is an investigator of the Howard Hughes Medical Institute. G.L., S.A.J., and B.G. are employees of GlaxoSmithKline. ",
year = "2005",
month = oct,
doi = "10.1016/j.cmet.2005.09.001",
language = "English (US)",
volume = "2",
pages = "217--225",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}