title: Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice.
abstract: Mitochondrial dysfunction in skeletal muscle has been implicated in the development of type 2 diabetes. However, whether these changes are a cause or a consequence of insulin resistance is not clear. We investigated the structure and function of muscle mitochondria during the development of insulin resistance and progression to diabetes in mice fed a high-fat, high-sucrose diet. Although 1 month of high-fat, high-sucrose diet feeding was sufficient to induce glucose intolerance, mice showed no evidence of mitochondrial dysfunction at this stage. However, an extended diet intervention induced a diabetic state in which we observed altered mitochondrial biogenesis, structure, and function in muscle tissue. We assessed the role of oxidative stress in the development of these mitochondrial abnormalities and found that diet-induced diabetic mice had an increase in ROS production in skeletal muscle. In addition, ROS production was associated with mitochondrial alterations in the muscle of hyperglycemic streptozotocin-treated mice, and normalization of glycemia or antioxidant treatment decreased muscle ROS production and restored mitochondrial integrity. Glucose- or lipid-induced ROS production resulted in mitochondrial alterations in muscle cells in vitro, and these effects were blocked by antioxidant treatment. These data suggest that mitochondrial alterations do not precede the onset of insulin resistance and result from increased ROS production in muscle in diet-induced diabetic mice.
authors.affiliation: INSERM, U870, IFR62, Oullins, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bonnard
authors.forename: Annie
authors.initials: A
authors.lastname: Durand
authors.forename: Simone
authors.initials: S
authors.lastname: Peyrol
authors.forename: Emilie
authors.initials: E
authors.lastname: Chanseaume
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Chauvin
authors.forename: Béatrice
authors.initials: B
authors.lastname: Morio
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D004041:Dietary Fats; D017382:Reactive Oxygen Species; D013395:Sucrose