title: FGF21 Mediates the Thermogenic and Insulin-Sensitizing Effects of Dietary Methionine Restriction but Not Its Effects on Hepatic Lipid Metabolism.
abstract: Dietary methionine restriction (MR) produces a rapid and persistent remodeling of white adipose tissue (WAT), an increase in energy expenditure (EE), and enhancement of insulin sensitivity. Recent work established that hepatic expression of FGF21 is robustly increased by MR.Fgf21-/-mice were used to test whether FGF21 is an essential mediator of the physiological effects of dietary MR. The MR-induced increase in energy intake and EE and activation of thermogenesis in WAT and brown adipose tissue were lost inFgf21-/-mice. However, dietary MR produced a comparable reduction in body weight and adiposity in both genotypes because of a negative effect of MR on energy intake inFgf21-/-mice. Despite the similar loss in weight, dietary MR produced a more significant increase in in vivo insulin sensitivity in wild-type than inFgf21-/-mice, particularly in heart and inguinal WAT. In contrast, the ability of MR to regulate lipogenic and integrated stress response genes in liver was not compromised inFgf21-/-mice. Collectively, these findings illustrate that FGF21 is a critical mediator of the effects of dietary MR on EE, remodeling of WAT, and increased insulin sensitivity but not of its effects on hepatic gene expression.
authors.affiliation: Department of Nutrition, Georgia State University, Atlanta, GA.
authors.forename: Desiree
authors.initials: D
authors.lastname: Wanders
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Forney
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA.
authors.forename: Kirsten P
authors.initials: KP
authors.lastname: Stone
authors.affiliation: Cell Biology & Bioimaging Core, Pennington Biomedical Research Center, Baton Rouge, LA.
authors.forename: David H
authors.initials: DH
authors.lastname: Burk
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Pierse
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA thomas.gettys@pbrc.edu.
authors.forename: Thomas W
authors.identifier: 0000-0001-7125-7995
authors.initials: TW
authors.lastname: Gettys
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015870:Gene Expression; D015309:Glucose Clamp Technique; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008715:Methionine