title: Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2.
abstract: FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months. Gcn2 KO mice recapitulate this phenotype, but LP-induced effects on food intake, EE, and body weight subsequently begin to appear after 14 days on diet. We show that this delayed emergence of LP-induced metabolic effects in Gcn2 KO mice coincides with a delayed but progressive increase of hepatic Fgf21 expression and blood FGF21 concentrations over time. These data indicate that FGF21 is essential for the metabolic response to protein restriction but that GCN2 is only transiently required for LP-induced FGF21.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laeger
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Albarado
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Burke
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Lexus
authors.initials: L
authors.lastname: Trosclair
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Hedgepeth
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Berthoud
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gettys
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Collier
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Electronic address: morriscd@pbrc.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D004044:Dietary Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases