Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution.
ChREBP
brown adipose tissue
cardiolipins
de novo lipogenesis
energy expenditure
fatty acid synthesis
fatty acids
lipidome
mitochondria
mitophagy
non-shivering thermogenesis
phospholipids
thermoneutrality
triacylglycerols
whitening
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
received:
01
07
2020
revised:
20
11
2020
accepted:
18
12
2020
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
5
1
2022
Statut:
ppublish
Résumé
Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans.
Identifiants
pubmed: 33440156
pii: S2211-1247(20)31613-2
doi: 10.1016/j.celrep.2020.108624
pmc: PMC8240962
mid: NIHMS1714850
pii:
doi:
Substances chimiques
Fatty Acids
0
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
108624Subventions
Organisme : NIDDK NIH HHS
ID : F32 DK102320
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK111714
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
Sci Rep. 2017 May 17;7(1):2060
pubmed: 28515468
Mol Metab. 2017 Nov;6(11):1381-1394
pubmed: 29107286
Nature. 2012 Apr 19;484(7394):333-8
pubmed: 22466288
Biophys J. 1997 Oct;73(4):1954-66
pubmed: 9336191
Cell Metab. 2018 Oct 2;28(4):644-655.e4
pubmed: 30033199
Biochim Biophys Acta. 1981 Jun 23;664(3):549-60
pubmed: 7272321
Lipids. 2008 Nov;43(11):1039-51
pubmed: 18763007
J Lipid Res. 2009 Aug;50(8):1600-8
pubmed: 19001357
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18691-18699
pubmed: 31451658
Nat Rev Endocrinol. 2017 Aug;13(8):458-465
pubmed: 28497813
Diabetes. 2009 Jul;58(7):1526-31
pubmed: 19401428
Cell Metab. 2018 Jan 9;27(1):195-209.e6
pubmed: 29153407
Nat Rev Mol Cell Biol. 2015 Nov;16(11):678-89
pubmed: 26490400
Biochem Biophys Res Commun. 2010 Oct 29;401(4):561-7
pubmed: 20888798
FASEB J. 2009 Sep;23(9):3113-20
pubmed: 19417078
Am J Physiol Endocrinol Metab. 2017 Jan 1;312(1):E72-E87
pubmed: 27923808
Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1415-24
pubmed: 21841017
Autophagy. 2015 Apr 3;11(4):643-52
pubmed: 25919711
Cell Metab. 2009 Feb;9(2):203-9
pubmed: 19187776
Lipids Health Dis. 2006 Jan 23;5:2
pubmed: 16430781
Proc Natl Acad Sci U S A. 2004 May 11;101(19):7281-6
pubmed: 15118080
J Lipid Res. 2007 Jul;48(7):1559-70
pubmed: 17426348
Best Pract Res Clin Endocrinol Metab. 2016 Aug;30(4):487-496
pubmed: 27697210
Curr Opin Clin Nutr Metab Care. 2012 Mar;15(2):122-6
pubmed: 22248591
Sci Signal. 2018 Apr 24;11(527):
pubmed: 29692364
Cell Metab. 2017 Aug 1;26(2):324-341
pubmed: 28768172
Am J Physiol Endocrinol Metab. 2017 Nov 1;313(5):E515-E527
pubmed: 28679625
Autophagy. 2011 Oct;7(10):1093-4
pubmed: 21993240
Endocr Rev. 2020 Jan 1;41(1):
pubmed: 31638161
J Biol Chem. 2019 Aug 9;294(32):12020-12039
pubmed: 31209110
Physiol Rev. 2004 Jan;84(1):277-359
pubmed: 14715917
J Clin Invest. 2013 Aug;123(8):3395-403
pubmed: 23867626
Eur J Nucl Med Mol Imaging. 2002 Oct;29(10):1393-8
pubmed: 12271425
Mol Metab. 2019 Aug;26:1-3
pubmed: 31155502
Acta Pharmacol Sin. 2013 May;34(5):625-35
pubmed: 23524572
Int J Cell Biol. 2014;2014:709828
pubmed: 24578708
Cell Rep. 2013 Dec 12;5(5):1196-203
pubmed: 24290753
J Lipid Res. 2015 Oct;56(10):1901-11
pubmed: 26293158
N Engl J Med. 2009 Apr 9;360(15):1500-8
pubmed: 19357405
J Clin Invest. 2020 May 1;130(5):2209-2219
pubmed: 31961826
J Biol Chem. 2020 Feb 14;295(7):1926-1942
pubmed: 31914415
Biochemistry. 2007 May 29;46(21):6417-28
pubmed: 17487985
Cell Rep. 2017 Oct 24;21(4):1021-1035
pubmed: 29069585
Nat Med. 2011 Feb;17(2):200-5
pubmed: 21258337
Biochim Biophys Acta. 1998 Nov 10;1376(3):353-68
pubmed: 9804988
Curr Opin Lipidol. 2012 Jun;23(3):190-5
pubmed: 22449813
Cell. 2020 Jan 9;180(1):135-149.e14
pubmed: 31883797
Cell Rep. 2020 Apr 14;31(2):107501
pubmed: 32294435
Biophys J. 1997 Sep;73(3):1492-505
pubmed: 9284316
Nat Commun. 2013;4:1528
pubmed: 23443556
Nat Rev Endocrinol. 2017 Dec;13(12):710-730
pubmed: 28849786
Nat Med. 2018 Mar;24(3):292-303
pubmed: 29400713
Cell Metab. 2016 Sep 13;24(3):402-419
pubmed: 27568548
Trends Endocrinol Metab. 2012 Feb;23(2):65-72
pubmed: 22154484
Nat Cell Biol. 2013 Jun;15(6):659-67
pubmed: 23624403
J Endocrinol. 2020 Jun;245(3):343-356
pubmed: 32208359
Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52
pubmed: 17473055
Am J Physiol Endocrinol Metab. 2019 Mar 1;316(3):E487-E503
pubmed: 30576247
J Lipid Res. 2014 Nov;55(11):2276-86
pubmed: 25193997
Cell Metab. 2015 Jan 6;21(1):33-8
pubmed: 25565203
Lipids. 2018 Jan;53(1):133-142
pubmed: 29488636
Adv Nutr. 2018 May 1;9(3):247-262
pubmed: 29767698
Mol Metab. 2018 Jan;7:161-170
pubmed: 29122558
Exp Physiol. 2020 Aug;105(8):1191-1200
pubmed: 32378255
Cell. 2018 Nov 29;175(6):1561-1574.e12
pubmed: 30449620
Metabolites. 2016 Aug 17;6(3):
pubmed: 27548241
N Engl J Med. 2009 Apr 9;360(15):1509-17
pubmed: 19357406
Eur J Biochem. 1997 Jan 15;243(1-2):240-6
pubmed: 9030745
Nat Cell Biol. 2013 Oct;15(10):1197-1205
pubmed: 24036476
J Biol Chem. 2003 Sep 26;278(39):37099-111
pubmed: 12842871
N Engl J Med. 2009 Apr 9;360(15):1518-25
pubmed: 19357407
Nat Metab. 2019 Aug;1(8):830-843
pubmed: 32694768