Adipose-Specific Deletion of TFAM Increases Mitochondrial Oxidation and Protects Mice against Obesity and Insulin Resistance

被引：204

作者：

Vernochet, Cecile ^{[1
]}

Mourier, Arnaud ^{[2
]}

Bezy, Olivier ^{[1
,8
]}

Macotela, Yazmin ^{[1
,9
]}

Boucher, Jeremie ^{[1
]}

Rardin, Matthew J. ^{[3
]}

An, Ding ^{[1
]}

Lee, Kevin Y. ^{[1
]}

Ilkayeva, Olga R. ^{[4
]}

Zingaretti, Cristina M. ^{[5
,6
]}

Emanuelli, Brice ^{[1
]}

Smyth, Graham ^{[1
]}

Cinti, Saverio ^{[5
,6
,7
]}

Newgard, Christopher B. ^{[4
]}

Gibson, Bradford W. ^{[3
]}

Larsson, Nils-Goeran ^{[2
]}

Kahn, Ronald ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA

[2] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

[3] Buck Inst Res Aging, Novato, CA 94945 USA

[4] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA

[5] United Hosp Ancona, Department Expt & Clin Med, I-60020 Ancona, Italy

[6] United Hosp Ancona, Diagnost Electron Microscopy Unit, I-60020 Ancona, Italy

[7] IRCCS San Raffaele Pisana, Adipose Organ Lab, I-00163 Rome, Italy

[8] Pfizer, Cardiovasc Metab & Endocrine Dis, Cambridge, MA 02139 USA

[9] UNAM, Inst Neurobiol, Queretaro 76230, Mexico

来源：

CELL METABOLISM | 2012年 / 16卷 / 06期

关键词：

ELECTRON-TRANSPORT CHAIN; SKELETAL-MUSCLE; KNOCKOUT MICE; COMPLEX-I; GENE-EXPRESSION; TISSUE; WHITE; FAT; DYSFUNCTION; PGC-1-ALPHA;

D O I：

10.1016/j.cmet.2012.10.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：765 / 776

页数：12

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