Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance
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Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. / Vernochet, Cecile; Mourier, Arnaud; Bezy, Olivier; Macotela, Yazmin; Boucher, Jeremie; Rardin, Matthew J; An, Ding; Lee, Kevin Y; Ilkayeva, Olga R; Zingaretti, Cristina M; Emanuelli, Brice; Smyth, Graham; Cinti, Saverio; Newgard, Christopher B; Gibson, Bradford W; Larsson, Nils-Göran; Kahn, C Ronald.
In: Cell Metabolism, Vol. 16, No. 6, 05.12.2012, p. 765-76.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance
AU - Vernochet, Cecile
AU - Mourier, Arnaud
AU - Bezy, Olivier
AU - Macotela, Yazmin
AU - Boucher, Jeremie
AU - Rardin, Matthew J
AU - An, Ding
AU - Lee, Kevin Y
AU - Ilkayeva, Olga R
AU - Zingaretti, Cristina M
AU - Emanuelli, Brice
AU - Smyth, Graham
AU - Cinti, Saverio
AU - Newgard, Christopher B
AU - Gibson, Bradford W
AU - Larsson, Nils-Göran
AU - Kahn, C Ronald
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/12/5
Y1 - 2012/12/5
N2 - Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity.
AB - Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity.
KW - Adipose Tissue, Brown
KW - Adipose Tissue, White
KW - Animals
KW - Cell Line
KW - DNA, Mitochondrial
KW - DNA-Binding Proteins
KW - Electron Transport Complex I
KW - Energy Metabolism
KW - Insulin Resistance
KW - Mice
KW - Mice, Knockout
KW - Mitochondria
KW - Mitochondrial Proteins
KW - Obesity
KW - Oxidative Phosphorylation
KW - Oxygen
KW - Transcription Factors
U2 - 10.1016/j.cmet.2012.10.016
DO - 10.1016/j.cmet.2012.10.016
M3 - Journal article
C2 - 23168219
VL - 16
SP - 765
EP - 776
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -
ID: 123351314