FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism.
Adipose Tissue
/ metabolism
Animals
Brain
/ metabolism
Diet, High-Fat
/ adverse effects
Diet, Protein-Restricted
Feeding Behavior
Fibroblast Growth Factors
/ genetics
Food Preferences
/ physiology
Glucose Intolerance
/ metabolism
Insulin Resistance
Klotho Proteins
Liver
/ metabolism
Male
Membrane Proteins
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ metabolism
FGF21
Klb
central nervous system
dietary protein restriction
macronutrient
nutrition
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
04 06 2019
04 06 2019
Historique:
received:
04
03
2019
revised:
05
04
2019
accepted:
03
05
2019
entrez:
6
6
2019
pubmed:
6
6
2019
medline:
6
8
2020
Statut:
ppublish
Résumé
Reduced dietary protein intake induces adaptive physiological changes in macronutrient preference, energy expenditure, growth, and glucose homeostasis. We demonstrate that deletion of the FGF21 co-receptor βKlotho (Klb) from the brain produces mice that are unable to mount a physiological response to protein restriction, an effect that is replicated by whole-body deletion of FGF21. Mice forced to consume a low-protein diet exhibit reduced growth, increased energy expenditure, and a resistance to diet-induced obesity, but the loss of FGF21 signaling in the brain completely abrogates that response. When given access to a higher protein alternative, protein-restricted mice exhibit a shift toward protein-containing foods, and central FGF21 signaling is essential for that response. FGF21 is an endocrine signal linking the liver and brain, which regulates adaptive, homeostatic changes in metabolism and feeding behavior during protein restriction.
Identifiants
pubmed: 31167139
pii: S2211-1247(19)30633-3
doi: 10.1016/j.celrep.2019.05.022
pmc: PMC6579533
mid: NIHMS1531057
pii:
doi:
Substances chimiques
FGF21 protein, human
0
Klb protein, mouse
0
Membrane Proteins
0
fibroblast growth factor 21
0
Fibroblast Growth Factors
62031-54-3
Klotho Proteins
EC 3.2.1.31
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2934-2947.e3Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK092587
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK115137
Pays : United States
Organisme : NIH HHS
ID : S10 OD023703
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI138136
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK072476
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105032
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK047348
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM118430
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
Biochim Biophys Acta. 2000 Jun 21;1492(1):203-6
pubmed: 10858549
Physiol Behav. 2000 Jun 1-15;69(4-5):383-9
pubmed: 10913775
Genesis. 2001 Sep;31(1):37-42
pubmed: 11668676
Physiol Biochem Zool. 2003 Mar-Apr;76(2):256-61
pubmed: 12794679
J Clin Invest. 2005 Jun;115(6):1627-35
pubmed: 15902306
JAMA. 2006 Apr 5;295(13):1539-48
pubmed: 16595757
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7432-7
pubmed: 17452648
Obesity (Silver Spring). 2008 Mar;16(3):566-71
pubmed: 18239565
Endocrinology. 2008 Dec;149(12):6018-27
pubmed: 18687777
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R866-76
pubmed: 19091911
Nutr Res Rev. 1997 Jan;10(1):151-79
pubmed: 19094262
Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10853-8
pubmed: 19541642
Diabetes. 2010 Jul;59(7):1817-24
pubmed: 20357365
Am J Physiol Regul Integr Comp Physiol. 2012 Apr 15;302(8):R917-28
pubmed: 22319049
Cell Metab. 2012 Sep 5;16(3):387-93
pubmed: 22958921
Elife. 2012 Oct 15;1:e00065
pubmed: 23066506
Obesity (Silver Spring). 2013 Jan;21(1):85-92
pubmed: 23404943
Nat Med. 2013 Sep;19(9):1153-6
pubmed: 23933983
Nat Med. 2013 Sep;19(9):1147-52
pubmed: 23933984
Cell Metab. 2013 Sep 3;18(3):333-40
pubmed: 24011069
Mol Metab. 2012 Aug 28;2(1):31-7
pubmed: 24024127
Annu Rev Physiol. 2014;76:519-33
pubmed: 24111557
Obes Rev. 2014 Mar;15(3):183-91
pubmed: 24588967
Cell Metab. 2014 Mar 4;19(3):418-30
pubmed: 24606899
Mol Metab. 2013 Dec 27;3(3):221-9
pubmed: 24749049
Am J Physiol Regul Integr Comp Physiol. 2014 Aug 1;307(3):R310-20
pubmed: 24898843
Diabetes. 2014 Dec;63(12):4057-63
pubmed: 25008183
Diabetes. 2014 Dec;63(12):4064-75
pubmed: 25024372
Cell Metab. 2014 Oct 7;20(4):670-7
pubmed: 25130400
J Clin Invest. 2014 Sep;124(9):3913-22
pubmed: 25133427
PLoS One. 2014 Nov 04;9(11):e111418
pubmed: 25369265
Mol Metab. 2014 Oct 08;4(1):51-7
pubmed: 25685689
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3481-6
pubmed: 25733862
FASEB J. 2015 Jun;29(6):2603-15
pubmed: 25742717
Trends Endocrinol Metab. 2015 May;26(5):256-62
pubmed: 25771038
Endocrinology. 2015 Jul;156(7):2470-81
pubmed: 25924103
Cell Metab. 2016 Feb 9;23(2):335-43
pubmed: 26724858
Cell Metab. 2016 Feb 9;23(2):344-9
pubmed: 26724861
Cell Metab. 2016 Mar 8;23(3):427-40
pubmed: 26959184
Am J Physiol Regul Integr Comp Physiol. 2016 May 15;310(10):R885-95
pubmed: 27030669
Metabolism. 2016 Jun;65(6):805-15
pubmed: 27173459
Cell Rep. 2016 Jul 12;16(2):520-530
pubmed: 27346343
Cell Rep. 2016 Jul 19;16(3):707-16
pubmed: 27396336
J Clin Invest. 2016 Sep 1;126(9):3263-78
pubmed: 27548521
Cell Metab. 2016 Oct 11;24(4):555-565
pubmed: 27693377
J Intern Med. 2017 Mar;281(3):233-246
pubmed: 27878865
Nat Rev Endocrinol. 2017 Feb;13(2):74-76
pubmed: 27983736
Appetite. 2018 Mar 1;122:26-31
pubmed: 28034739
Gastroenterology. 2017 May;152(7):1728-1738
pubmed: 28192106
Sci Rep. 2017 Apr 04;7:45819
pubmed: 28374855
Cell Metab. 2017 Apr 4;25(4):935-944.e4
pubmed: 28380381
Cell Metab. 2017 May 2;25(5):1045-1053.e6
pubmed: 28467924
Mol Metab. 2017 Jun 24;6(8):873-881
pubmed: 28752051
Sci Rep. 2017 Aug 15;7(1):8209
pubmed: 28811495
Cell Metab. 2017 Nov 7;26(5):709-718.e3
pubmed: 28988823
Cell Rep. 2017 Oct 10;21(2):403-416
pubmed: 29020627
Physiol Behav. 2018 Feb 1;184:235-241
pubmed: 29225095
J Physiol. 2018 Feb 15;596(4):623-645
pubmed: 29266268
Nature. 2018 Jan 25;553(7689):501-505
pubmed: 29342135
Diabetologia. 2018 Jun;61(6):1459-1469
pubmed: 29550873
Annu Rev Nutr. 2018 Aug 21;38:173-196
pubmed: 29727594
J Nutr. 2018 Jun 1;148(6):989-998
pubmed: 29878268
Front Neuroendocrinol. 2018 Oct;51:125-131
pubmed: 29890191
Nat Commun. 2018 Nov 2;9(1):4604
pubmed: 30389922
Endocrinology. 2019 May 1;160(5):1069-1080
pubmed: 30802283
J Nutr. 1982 Sep;112(9):1663-72
pubmed: 7108638
N Engl J Med. 1995 Mar 9;332(10):621-8
pubmed: 7632212
J Nutr. 1994 Aug;124(8):1152-60
pubmed: 8064364
Appetite. 1997 Jun;28(3):201-13
pubmed: 9218094