Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity.
BACKGROUND
Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals.


METHODS
Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions.


RESULTS
Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin.


CONCLUSIONS
Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults.
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
Elizaveta V
EV
Menshikova
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
Vladimir B
VB
Ritov
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
John J
JJ
Dube
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
Francesca
F
Amati
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
Maja
M
Stefanovic-Racic
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.
Frederico G S
FGS
Toledo
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Medical Research Institute, Orlando.
Paul M
PM
Coen
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Medical Research Institute, Orlando.
Bret H
BH
Goodpaster
D000368:Aged; D031204:Caloric Restriction; D004272:DNA, Mitochondrial / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss / Q000502:physiology*
D004272:DNA, Mitochondrial; D007328:Insulin
Caloric restriction; Glucose uptake; Human aging; Muscle metabolism; Obesity