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Diabetes Publish Ahead of Print published online ahead of print February 5, 2008
DOI: 10.2337/db07-1429

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Original Research

Mitochondrial capacity in skeletal muscle is not stimulated by weight loss, despite increases in insulin action and decreases in intramyocellular lipid content.

Frederico G.S. Toledo1, Elizabeth V. Menshikova1, Koichiro Azuma1, Zofia Radiková1, Carol A. Kelley1, Vladimir B. Ritov1, and David E. Kelley1

1Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Purpose: In obesity and type-2 diabetes, exercise combined with weight loss increases skeletal muscle mitochondrial capacity. It remains unclear whether mitochondrial capacity increases because of weight loss, improvements in IR or physical training. In this study, we examined the effects of an intervention of weight loss induced by diet and compared to a similar intervention of weight loss by diet with exercise. Both are known to improve IR, and we tested the hypothesis that physical activity, rather than improved IR, is required to increase mitochondrial capacity of muscle.

Methods: 16 sedentary overweight/obese volunteers were randomized to a 16-week intervention of diet (D) (n=7) or diet+exercise (D+E) (n=9). Insulin sensitivity was measured using euglycemic clamps. Mitochondria were examined in muscle biopsies before and after intervention. We measured mitochondrial content and size by electron microscopy, electron transport chain (ETC) activity, cardiolipin content and mtDNA content. Intra-myocellular content of lipid (IMCL) and fiber-type distribution were determined by histology.

Results: D and D+E achieved similar weight loss (10.8% and 9.2%, respectively); only D+E improved aerobic capacity. Insulin sensitivity improved similarly in both groups. Mitochondrial content and ETC activity increased following D+E, but remained unchanged following D, and mitochondrial size decreased with weight loss despite improvement in IR. IMCL decreased in D, but not in the D+E intervention.

Conclusions: Despite similar effects to improve IR, these interventions had differential effects on mitochondria. Clinically-significant weight loss in the absence of increased physical activity ameliorates IR and IMCL, but does not increase muscle mitochondrial capacity in obesity.


Key Words: mitochondria • insulin resistance • skeletal muscle • obesity


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