Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling.
futile cycle
malate aspartate shuttle
metabolism
mitochondrial pyruvate carrier
thermogenesis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 12 2020
03 12 2020
Historique:
received:
12
11
2019
revised:
15
09
2020
accepted:
07
10
2020
pubmed:
5
12
2020
medline:
28
4
2021
entrez:
4
12
2020
Statut:
ppublish
Résumé
Combined fatty acid esterification and lipolysis, termed lipid cycling, is an ATP-consuming process that contributes to energy expenditure. Therefore, interventions that stimulate energy expenditure through lipid cycling are of great interest. Here we find that pharmacological and genetic inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes activates lipid cycling and energy expenditure, even in the absence of adrenergic stimulation. We show that the resulting increase in ATP demand elevates mitochondrial respiration coupled to ATP synthesis and fueled by lipid oxidation. We identify that glutamine consumption and the Malate-Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). We thus demonstrate that energy expenditure through enhanced lipid cycling can be activated in brown adipocytes by decreasing mitochondrial pyruvate availability. We present a new mechanism to increase energy expenditure and fat oxidation in brown adipocytes, which does not require adrenergic stimulation of mitochondrial uncoupling.
Identifiants
pubmed: 33275313
doi: 10.15252/embr.201949634
pmc: PMC7726774
doi:
Substances chimiques
Lipids
0
Uncoupling Protein 1
0
Pyruvic Acid
8558G7RUTR
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
e49634Subventions
Organisme : MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
ID : 404153/2016-0
Organisme : Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
ID : E-26/203.043/2016
Organisme : Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
ID : E-26/102.333/2013
Organisme : UC | UCSF | Clinical and Translational Science Institute, University of California, San Francisco (CTSI)
ID : UL1TR001881
Organisme : NIAAA NIH HHS
ID : R01 AA026914
Pays : United States
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : 5 R01 DK099618‐02
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : P30 41301
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009056
Pays : United States
Organisme : MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
ID : 229526/2013-6
Organisme : MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
ID : 303044/2017-9
Organisme : NIGMS NIH HHS
ID : R35 GM138003
Pays : United States
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
ID : 001
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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