期刊
PLOS ONE
卷 8, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0056719
关键词
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资金
- KU Leuven [GOA 2008/16]
- Flanders Fund for Scientific Research (FWO) [G.0733-09, G.0672-12]
- National Institutes of Health (USA) [HL-076440]
- MRC [G0600717, MC_UU_12012/5] Funding Source: UKRI
- Medical Research Council [G0600717, MC_UU_12012/5/B, MC_UU_12012/5, G0600717B] Funding Source: researchfish
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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