title: Characteristics of skeletal muscle mitochondrial biogenesis induced by moderate-intensity exercise and weight loss in obesity.
abstract: There are fewer mitochondria and a reduced oxidative capacity in skeletal muscle in obesity. Moderate-intensity physical activity combined with weight loss increase oxidative enzyme activity in obese sedentary adults; however, this adaptation occurs without a significant increase in mitochondrial DNA (mtDNA), which is unlike the classic pattern of mitochondrial biogenesis induced by vigorous activity. The objective of this study was to examine the hypothesis that the mitochondrial adaptation to moderate-intensity exercise and weight loss in obesity induces increased mitochondrial cristae despite a lack of mtDNA proliferation. Content of cardiolipin and mtDNA and enzymatic activities of the electron transport chain (ETC) and tricarboxylic acid cycle were measured in biopsy samples of vastus lateralis muscle obtained from sedentary obese men and women before and following a 4-mo walking intervention combined with weight loss. Cardiolipin increased by 60% from 47 +/- 4 to 74 +/- 8 microg/mU CK (P < 0.01), but skeletal muscle mtDNA content did not change significantly (1,901 +/- 363 to 2,169 +/- 317 Rc, where Rc is relative copy number of mtDNA per diploid nuclear genome). Enzyme activity of the ETC increased (P < 0.01); that for rotenone-sensitive NADH-oxidase (96 +/- 1%) increased more than for ubiquinol-oxidase (48 +/- 6%). Activities for citrate synthase and succinate dehydrogenase increased by 29 +/- 9% and 40 +/- 6%, respectively. In conclusion, moderate-intensity physical activity combined with weight loss induces skeletal muscle mitochondrial biogenesis in previously sedentary obese men and women, but this response occurs without mtDNA proliferation and may be characterized by an increase in mitochondrial cristae.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Menshikova
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Ritov
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Koichiro
authors.initials: K
authors.lastname: Azuma
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D002308:Cardiolipins / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002952:Citric Acid Cycle; D004272:DNA, Mitochondrial / Q000378:metabolism; D018752:Diet, Fat-Restricted; D042967:Electron Transport Complex I / Q000378:metabolism; D002149:Energy Intake; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000378:metabolism; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D002308:Cardiolipins; D004272:DNA, Mitochondrial; D010088:Oxidoreductases; C432586:ubiquinol oxidase; D013385:Succinate Dehydrogenase; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I