title: The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging.
abstract: Mitochondria within skeletal muscle have been implicated in insulin resistance of obesity and type 2 diabetes mellitus as well as impaired muscle function with normal aging. Evaluating the potential of interventions to improve mitochondria is clearly relevant to the prevention or treatment of metabolic diseases and age-related dysfunction. This review provides an overview and critical evaluation of the effects of weight loss and exercise interventions on skeletal muscle mitochondria, along with implications for insulin resistance, obesity, type 2 diabetes and aging. The available literature strongly suggests that the lower mitochondrial capacity associated with obesity, type 2 diabetes and aging is not an irreversible lesion. However, weight loss does not appear to affect this response, even when the weight loss is extreme. In contrast, increasing physical activity improves mitochondrial content and perhaps the function of individual mitochondrion. Despite the consistent effect of exercise to improve mitochondrial capacity, studies mechanistically linking mitochondria to insulin resistance, reductions in intramyocellular lipid or improvement in muscle function remain inconclusive. In summary, studies of diet and exercise training have advanced our understanding of the link between mitochondrial oxidative capacity and insulin resistance in obesity, type 2 diabetes and aging. Nevertheless, additional inquiry is necessary to establish the significance and clinical relevance of those perturbations, which could lead to targeted therapies for a myriad of conditions and diseases involving mitochondria.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Frederico G S
authors.initials: FG
authors.lastname: Toledo
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D015444:Exercise; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D015431:Weight Loss
keywords: Exercise; Mitochondria; Obesity; Physical activity; Skeletal muscle; Weight loss