Mice Deficient in the Respiratory Chain Gene Cox6a2 Are Protected against High-Fat Diet-Induced Obesity and Insulin Resistance

Quintens, Roel; Singh, Sarvjeet; Lemaire, Katleen; De Bock, Katrien; Granvik, Mikaela; Schraenen, Anica; Vroegrijk, Irene Olga Cornelia Maria; Costa, Veronica; Van Noten, Pieter; Lambrechts, Dennis; Lehnert, Stefan; Van Lommel, Leentje; Thorrez, Lieven; De Faudeur, Geoffroy; Romijn, Johannes Anthonius; Shelton, John Michael; Scorrano, Luca; Lijnen, Henri Roger; Voshol, Peter Jacobus; Carmeliet, Peter
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


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