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23460811
Mice deficient in the respiratory chain gene Cox6a2 are protected against high-fat diet-induced obesity and insulin resistance.

PLoS One, 2013;8(2):e56719.

Quintens R[1], Singh S, Lemaire K, De Bock K, Granvik M, Schraenen A, Vroegrijk IO, Costa V, Van Noten P, Lambrechts D, Lehnert S, Van Lommel L, Thorrez L, De Faudeur G, Romijn JA, Shelton JM, Scorrano L, Lijnen HR, Voshol PJ, Carmeliet P, Mammen PP, Schuit F

Affiliations

PMID: 23460811DOI: 10.1371/journal.pone.0056719

Impact factor: 3.752

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.
MeSH terms
AMP-Activated Protein Kinases; Animals; Body Weight; Diet, High-Fat; Electron Transport; Electron Transport Complex IV; Energy Metabolism; Enzyme Activation; Glucose Tolerance Test; In Vitro Techniques; Insulin; Insulin Resistance; Ion Channels; Mice; Mitochondrial Proteins; Mitochondrial Size; Models, Biological; Muscle Fatigue; Muscle Proteins; Muscle, Skeletal; Obesity; Reactive Oxygen Species; Starvation; Thermogenesis; Thinness; Uncoupling Protein 1
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