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1 Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
2 Department of Human Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: kelley{at}msx.dept-med.pitt.edu.
The current study was undertaken to address responsiveness of skeletal muscle mitochondrial ETC activity to weight loss (WL) and exercise in overweight or obese, sedentary volunteers. Fourteen middle-aged participants (7 M / 7 W) had assessments of mitochondrial electron transport chain (ETC) activity and mtDNA in vastus lateralis muscle, obtained by percutaneous biopsy, before and following a 16 week intervention. Mean WL was 9.7±1.5% and the mean increase in VO2max was 21.7±3.7%. Total ETC activity, increased significantly, from 0.13±0.02 to 0.19±0.03 U/mU CK (p<0.001). ETC activity was also assessed in mitochondria isolated into sub-sarcolemmal (SSM) and inter-myofibrillar (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 versus 22±2%), despite the increase in ETC activity. Also, muscle mtDNA content did not change significantly (1665±213 versus 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 VO2max. 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 weight loss and improved aerobic capacity contributes to associated alleviation of insulin resistance.
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