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.
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cecile
authors.initials: C
authors.lastname: Vernochet
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.forename: Olivier
authors.initials: O
authors.lastname: Bezy
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Macotela
authors.forename: Jeremie
authors.initials: J
authors.lastname: Boucher
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rardin
authors.forename: Ding
authors.initials: D
authors.lastname: An
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lee
authors.forename: Olga R
authors.initials: OR
authors.lastname: Ilkayeva
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Zingaretti
authors.forename: Brice
authors.initials: B
authors.lastname: Emanuelli
authors.forename: Graham
authors.initials: G
authors.lastname: Smyth
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Gibson
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D004734:Energy Metabolism; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D042967:Electron Transport Complex I; D010100:Oxygen