Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity
Abstract
The current study was undertaken to address responsiveness of skeletal muscle mitochondrial electron transport chain (ETC) activity to weight loss (WL) and exercise in overweight or obese, sedentary volunteers. Fourteen middle-aged participants (7 male/7 female) had assessments of mitochondrial ETC activity and mitochondrial (mt)DNA in vastus lateralis muscle, obtained by percutaneous biopsy, before and after a 16-wk intervention. Mean WL was 9.7 (1.5%) and the mean increase in V̇o 2 max was [means (SD)] 21.7 (3.7)%. Total ETC activity increased significantly, from 0.13 (0.02) to 0.19 (0.03) U/mU creatine kinase (CK; P < 0.001). ETC activity was also assessed in mitochondria isolated into subsarcolemmal (SSM) and intermyofibrillar (IMF-M) fractions. In response to intervention, there was a robust increase of ETC activity in SSM (0.028 (0.007) to 0.046 (0.011) U/mU CK, P < 0.001), and in IMF-M [0.101 (0.015) to 0.148 (0.018) U/mU CK, P < 0.005]. At baseline, the percentage of ETC activity contained in the SSM fraction was low and remained unchanged following intervention [19 ( 3 ) vs. 22 ( 2 )%], despite the increase in ETC activity. Also, muscle mtDNA content did not change significantly [1665 (213) vs. 1874 (214) mtDNA/nuclear DNA], denoting functional improvement rather than proliferation of mitochondria as the principal mechanism of enhanced ETC activity. Increases in ETC activity were correlated with energy expenditure during exercise sessions, and ETC activity in SSM correlated with insulin sensitivity after adjustment for V̇o 2 max. In summary, skeletal muscle ETC activity is increased by WL and exercise in previously sedentary obese men and women. We conclude that improved skeletal muscle ETC activity following moderate WL and improved aerobic capacity contributes to associated alleviation of insulin resistance.
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Exercise-induced improvement in insulin sensitivity is associated with improved muscle oxidative capacity and increased mitochondrial density and activity.
“the improvement in insulin sensitivity following exercise is associated with improved muscle oxidative capacity [125, 126] and increases in both mitochondrial density [127] and activity [128–130]”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [129]
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- Authors
- Menshikova, E. V., Ritov, V. B., Toledo, F. G. S., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E.
- Affiliations
- University of Pittsburgh (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2005-04
- Volume
- 288
- Issue
- 4
- Pages
- E818-E825
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2055029667
- Cited by
- 189
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 19 · 2012: 17
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK-462, DK-49200-08, R01DK049200)
- National Center for Research Resources (M01RR000056, 5 M01 RR00056)
- NIH Clinical Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- weight loss, physical activity, skeletal muscle, mitochondrial electron transport chain, obesity, mitochondrial DNA, vastus lateralis, subsarcolemmal mitochondria, interfibrillar mitochondria, cardiorespiratory fitness, energy expenditure, insulin sensitivity, insulin resistance, sedentary adults
- MeSH terms
- Adult, DNA, Mitochondrial, Electron Transport, Female, Humans, Insulin Resistance, Male, Mitochondria, Muscle, Obesity, Sarcolemma, Cohort Studies, Weight Loss, Exercise, Polymerase Chain Reaction, Muscle, Skeletal, Microscopy, Electron, Transmission
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