title: Mice deficient in the respiratory chain gene Cox6a2 are protected against high-fat diet-induced obesity and insulin resistance.
abstract: Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance.
authors: Gene Expression Unit, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Roel
authors: R
authors: Quintens
authors: Sarvjeet
authors: S
authors: Singh
authors: Katleen
authors: K
authors: Lemaire
authors: Katrien
authors: K
authors: De Bock
authors: Mikaela
authors: M
authors: Granvik
authors: Anica
authors: A
authors: Schraenen
authors: Irene Olga Cornelia Maria
authors: IO
authors: Vroegrijk
authors: Veronica
authors: V
authors: Costa
authors: Pieter
authors: P
authors: Van Noten
authors: Dennis
authors: D
authors: Lambrechts
authors: Stefan
authors: S
authors: Lehnert
authors: Leentje
authors: L
authors: Van Lommel
authors: Lieven
authors: L
authors: Thorrez
authors: Geoffroy
authors: G
authors: De Faudeur
authors: Johannes Anthonius
authors: JA
authors: Romijn
authors: John Michael
authors: JM
authors: Shelton
authors: Luca
authors: L
authors: Scorrano
authors: Henri Roger
authors: HR
authors: Lijnen
authors: Peter Jacobus
authors: PJ
authors: Voshol
authors: Peter
authors: P
authors: Carmeliet
authors: Pradeep Puthenveetil Abraham
authors: PP
authors: Mammen
authors: Frans
authors: F
authors: Schuit
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004579:Electron Transport / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D053142:Mitochondrial Size / Q000187:drug effects; D008954:Models, Biological; D018763:Muscle Fatigue / Q000187:drug effects; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013217:Starvation / Q000473:pathology; D022722:Thermogenesis / Q000187:drug effects; D013851:Thinness / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; C472628:Cox6a1 protein, mouse; C583181:Cox6a2 protein, mouse; D003576:Electron Transport Complex IV; D055372:AMP-Activated Protein Kinases