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

PloS One
Roel QuintensFrans C Schuit

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.

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Related Concepts

Metabolic Process, Cellular
Diabetes Mellitus, Non-Insulin-Dependent
Brown Fat
Biochemical Pathway
Thyrotropin Class in ATC
Glucagon (rDNA)
Cytochrome C Oxidase
Insulin Sensitivity
MED12 gene
Cytochrome c Oxidase Subunit VIa

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