Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance

Cecile Vernochet; Arnaud Mourier; Olivier Bezy; Yazmin Macotela; Jeremie Boucher; Matthew J Rardin; Ding An; Kevin Y Lee; Olga R Ilkayeva; Cristina M Zingaretti; Brice Emanuelli; Graham Smyth; Saverio Cinti; Christopher B Newgard; Bradford W Gibson; Nils-Göran Larsson; C Ronald Kahn

doi:10.1016/j.cmet.2012.10.016

Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance

Cecile Vernochet, Arnaud Mourier, Olivier Bezy, Yazmin Macotela, Jeremie Boucher, Matthew J Rardin, Ding An, Kevin Y Lee, Olga R Ilkayeva, Cristina M Zingaretti, Brice Emanuelli, Graham Smyth, Saverio Cinti, Christopher B Newgard, Bradford W Gibson, Nils-Göran Larsson, C Ronald Kahn

130 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Cell Metabolism
Volume	16
Issue number	6
Pages (from-to)	765-76
Number of pages	12
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2012.10.016
Publication status	Published - 5 Dec 2012

Keywords

Adipose Tissue, Brown
Adipose Tissue, White
Animals
Cell Line
DNA, Mitochondrial
DNA-Binding Proteins
Electron Transport Complex I
Energy Metabolism
Insulin Resistance
Mice
Mice, Knockout
Mitochondria
Mitochondrial Proteins
Obesity
Oxidative Phosphorylation
Oxygen
Transcription Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Vernochet, C., Mourier, A., Bezy, O., Macotela, Y., Boucher, J., Rardin, M. J., An, D., Lee, K. Y., Ilkayeva, O. R., Zingaretti, C. M., Emanuelli, B., Smyth, G., Cinti, S., Newgard, C. B., Gibson, B. W., Larsson, N-G., & Kahn, C. R. (2012). Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metabolism, 16(6), 765-76. https://doi.org/10.1016/j.cmet.2012.10.016

Vernochet, C, Mourier, A, Bezy, O, Macotela, Y, Boucher, J, Rardin, MJ, An, D, Lee, KY, Ilkayeva, OR, Zingaretti, CM, Emanuelli, B, Smyth, G, Cinti, S, Newgard, CB, Gibson, BW, Larsson, N-G & Kahn, CR 2012, 'Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance', Cell Metabolism, vol. 16, no. 6, pp. 765-76. https://doi.org/10.1016/j.cmet.2012.10.016

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title = "Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance",

abstract = "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.",

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AU - Vernochet, Cecile

AU - Mourier, Arnaud

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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

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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.

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KW - Energy Metabolism

KW - Insulin Resistance

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KW - Mice, Knockout

KW - Mitochondria

KW - Mitochondrial Proteins

KW - Obesity

KW - Oxidative Phosphorylation

KW - Oxygen

KW - Transcription Factors

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JO - Cell Metabolism

JF - Cell Metabolism

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Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance

Abstract

Keywords

UN SDGs

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