TY - JOUR
T1 - Mice Deficient in the Respiratory Chain Gene Cox6a2 Are Protected against High-Fat Diet-Induced Obesity and Insulin Resistance
AU - Quintens, Roel
AU - Singh, Sarvjeet
AU - Lemaire, Katleen
AU - de Bock, Katrien
AU - Granvik, Mikaela
AU - Schraenen, Anica
AU - Vroegrijk, Irene Olga Cornelia Maria
AU - Costa, Veronica
AU - van Noten, Pieter
AU - Lambrechts, Dennis
AU - Lehnert, Stefan
AU - Van Lommel, Leentje
AU - Thorrez, Lieven
AU - de Faudeur, Geoffroy
AU - Romijn, Johannes Anthonius
AU - Shelton, John Michael
AU - Scorrano, Luca
AU - Lijnen, Henri Roger
AU - Voshol, Peter Jacobus
AU - Carmeliet, Peter
AU - Mammen, Pradeep Puthenveetil Abraham
AU - Schuit, Frans
N1 - Copyright: 2013 Quintens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was financially supported by grants of the KU Leuven (GOA 2008/16 to FS), the Flanders Fund for Scientific Research (FWO grants G.0733-09
and G.0672-12 to FS) and the National Institutes of Health (USA, HL-076440 to PM). The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
PY - 2013/2/27
Y1 - 2013/2/27
N2 - 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.
AB - 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.
KW - Electron transport
KW - Energy metabolism
KW - Insulin resistance
UR - https://www.scopus.com/pages/publications/84874511732
U2 - 10.1371/journal.pone.0056719
DO - 10.1371/journal.pone.0056719
M3 - Article
C2 - 23460811
AN - SCOPUS:84874511732
SN - 1932-6203
VL - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 2
M1 - e56719
ER -