Mitochondrial capacity in skeletal muscle is not stimulated by weight loss despite increases in insulin action and decreases in intramyocellular lipid content.
OBJECTIVE
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 insulin resistance, or physical training. In this study, we examined the effects of an intervention of weight loss induced by diet and compared these with those of a similar intervention of weight loss by diet with exercise. Both are known to improve insulin resistance, and we tested the hypothesis that physical activity, rather than improved insulin resistance, is required to increase mitochondrial capacity of muscle.


METHODS
Sixteen sedentary overweight/obese volunteers were randomized to a 16-week intervention of diet (n = 7) or diet plus exercise (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 mitochondrial DNA content. Intramyocellular content of lipid (IMCL) and fiber-type distribution were determined by histology.


RESULTS
The diet-only and diet plus exercise groups achieved similar weight loss (10.8 and 9.2%, respectively); only the diet plus exercise group improved aerobic capacity. Insulin sensitivity improved similarly in both groups. Mitochondrial content and ETC activity increased following the diet plus exercise intervention but remained unchanged following the diet-only intervention, and mitochondrial size decreased with weight loss despite improvement in insulin resistance. IMCL decreased in the diet-only but not in the diet plus exercise intervention.


CONCLUSIONS
Despite similar effects to improve insulin resistance, these interventions had differential effects on mitochondria. Clinically significant weight loss in the absence of increased physical activity ameliorates insulin resistance and IMCL but does not increase muscle mitochondrial capacity in obesity.
Toledo
Frederico G S
FG
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. toledofs@upmc.edu
Menshikova
Elizabeth V
EV
Azuma
Koichiro
K
Radiková
Zofia
Z
Kelley
Carol A
CA
Ritov
Vladimir B
VB
Kelley
David E
DE
D002308:Cardiolipins / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D004038:Diet, Reducing; D015444:Exercise; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008019:Life Style; D008055:Lipids / Q000502:physiology*; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D050177:Overweight / Q000503:physiopathology*; D010101:Oxygen Consumption; D015431:Weight Loss / Q000502:physiology*
D002308:Cardiolipins; D004272:DNA, Mitochondrial; D007328:Insulin; D008055:Lipids