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Science 331 (6024): 1621-1624

Copyright © 2011 by the American Association for the Advancement of Science

FGF19 as a Postprandial, Insulin-Independent Activator of Hepatic Protein and Glycogen Synthesis

Serkan Kir,1 Sara A. Beddow,2 Varman T. Samuel,2 Paul Miller,3,* Stephen F. Previs,3,* Kelly Suino-Powell,4 H. Eric Xu,4 Gerald I. Shulman,2,5 Steven A. Kliewer,1,6,{dagger} David J. Mangelsdorf1,7,{dagger}

Abstract: Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.

1 Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
2 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
3 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
4 Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
5 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
6 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
7 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

* Present address: Exploratory Biomarkers, Atherosclerosis, Merck, 126 East Lincoln Avenue, Rahway, NJ 07065, USA.

{dagger} To whom correspondence should be addressed. E-mail: davo.mango{at}utsouthwestern.edu (D.J.M.); steven.kliewer{at}utsouthwestern.edu (S.A.K.)

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