Local acetate inhibits brown adipose tissue function.
Acetates
/ metabolism
Adipocytes, Brown
/ metabolism
Adipose Tissue, Brown
/ drug effects
Adipose Tissue, White
/ metabolism
Animals
Citric Acid Cycle
/ genetics
Diet, High-Fat
Eating
Energy Metabolism
/ drug effects
Gene Expression
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation
/ genetics
Male
Mice
Mice, Inbred C57BL
Obesity
/ metabolism
Thermogenesis
/ drug effects
Transcriptome
/ genetics
RNA-seq
acetate
brown adipose tissue
obesity
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
accepted:
03
11
2021
entrez:
30
11
2021
pubmed:
1
12
2021
medline:
19
1
2022
Statut:
ppublish
Résumé
Brown adipose tissue has been extensively studied in the last decade for its potential to counteract the obesity pandemic. However, the paracrine regulation within brown tissue is largely unknown. Here, we show that local acetate directly inhibits brown fat thermogenesis, without changing acetate levels in the circulation. We demonstrate that modulating acetate within brown tissue at physiological levels blunts its function and systemically decreases energy expenditure. Using a series of transcriptomic analyses, we identified genes related to the tricarboxylic acid cycle and brown adipocyte formation, which are down-regulated upon local acetate administration. Overall, these findings demonstrate that local acetate inhibits brown fat function.
Identifiants
pubmed: 34845033
pii: 2116125118
doi: 10.1073/pnas.2116125118
pmc: PMC8670478
pii:
doi:
Substances chimiques
Acetates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Nature. 2020 Nov;587(7832):98-102
pubmed: 33116305
Nat Commun. 2014 Apr 29;5:3611
pubmed: 24781306
Biochim Biophys Acta. 2013 May;1831(5):943-9
pubmed: 23353596
Nat Med. 2017 Dec;23(12):1454-1465
pubmed: 29131158
Cell Rep. 2018 Mar 13;22(11):2849-2859
pubmed: 29539415
Endocrinology. 2005 Dec;146(12):5092-9
pubmed: 16123168
Int J Obes (Lond). 2016 Jun;40(6):955-63
pubmed: 26975441
Sci Rep. 2019 Aug 29;9(1):12515
pubmed: 31467327
J Lipid Res. 1968 Jul;9(4):509-12
pubmed: 5725882
Cell Metab. 2014 Oct 7;20(4):670-7
pubmed: 25130400
Sci Rep. 2017 May 24;7(1):2360
pubmed: 28539646
Adipocyte. 2014 Apr 1;3(2):121-5
pubmed: 24719785
Cell. 2015 Oct 22;163(3):643-55
pubmed: 26496606
Cell Rep. 2020 Mar 10;30(10):3424-3433.e4
pubmed: 32160547
Nature. 2016 Jun 08;534(7606):213-7
pubmed: 27279214
Cell Metab. 2021 Jan 5;33(1):4-6
pubmed: 33406404
Cell. 2014 Jan 16;156(1-2):20-44
pubmed: 24439368