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Skeletal Muscle Metabolic Dysfunction in Obesity and Metabolic Syndrome

  • Greg D. Wells (a1), Michael D. Noseworthy (a2), Jill Hamilton (a3), Mark Tarnopolski (a4) and Ingrid Tein (a5)...


Obesity and the related metabolic syndrome have become a worldwide epidemic. Inactivity appears to be a primary causative factor in the pathogenesis of this obesity and metabolic syndrome. There are two possible, perhaps not mutually exclusive, events that may lead to intramyocellular lipid accumulation and mitochondrial dysfunction in patients with obesity. First, obesity, with high intake-associated lipid accumulation in muscle may interfere with cellular mitochondrial function through generation of reactive oxygen species leading to lipid membrane peroxidative injury and disruption of mitochondrial membrane-dependent enzymes. This in turn leads to impaired oxidative metabolism. Secondly, a primary defect in mitochondrial oxidative metabolism may be responsible for a reduction in fatty acid oxidation leading to intramyocellular lipid accumulation as a secondary event. Non-invasive techniques such as proton (1H) and phosphorus (31P) magnetic resonance spectroscopy, coupled with specific magnetic resonance imaging techniques, may facilitate the investigation of the effects of various ergometric interventions on the pathophysiology of obesity and the metabolic syndrome. Exercise has positive effects on glucose metabolism, aerobic metabolism, mitochondrial density, and respiratory chain proteins in patients with metabolic syndrome, and we propose that this may be due to the exercise effects on AMP kinase, and a prospective physiological mechanism for this benefit is presented. A physiological model of the effect of intramyocellular lipid accumulation on oxidative metabolism and insulin mediated glucose uptake is proposed.


L'obésité et le syndrome métabolique, deux entités qui sont reliées, sont devenus épidémiques à l'échelle mondiale. L'inactivité semble être le facteur causal primaire. Il existe deux possibilités, qui ne sont peut-être pas mutuellement exclusives, qui peuvent conduire à une accumulation intramyocellulaire de lipides et à une dysfonction mitochondriale chez les patients obèses. D'une part l'obésité, avec une accumulation musculaire de lipides suite à une consommation élevée de lipides, peut interférer avec la fonction mitochondriale à cause de la production de radicaux libres qui provoquent la peroxydation des lipides membranaires et la perturbation des enzymes mitochondriales dépendantes de la membrane entravant ainsi le métabolisme oxydatif. D'autre part, un défaut primaire dans le métabolisme oxydatif mitochondrial pourrait être responsable d'une diminution de l'oxydation des acides gras, ce qui entraîrait secondairement une accumulation lipidique intramyocellulaire. Des techniques non-effractives comme la spectroscopie RMN du proton (1H) et du phosphore (31P), couplées à des techniques spécifiques d'imagerie par résonance magnétique pourraient faciliter l'étude des effets de différentes interventions ergométriques sur la physiopathologie de l'obésité et du syndrome métabolique. L'exercice a des effets positifs sur le métabolisme du glucose, le métabolisme aérobique, la densité mitochondriale et les protéines de la chaî respiratoire chez les patients atteints du syndrome métabolique, ce qui porte à croire que l'exercice influence la kinase activée par l'AMP et nous proposons un mécanisme physiologique pour l'expliquer. Nous présentons également un modèle physiologique de l'effet de l'accumulation lipidique intramyocellulaire sur le métabolisme oxydatif et sur la captation du glucose médiée par l'insuline.

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