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. 2017 Dec 12;73(1):81-87.
doi: 10.1093/gerona/glw328.

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity

Elizaveta V Menshikova  1 , Vladimir B Ritov  1 , John J Dube  1 , Francesca Amati  1 , Maja Stefanovic-Racic  1 , Frederico G S Toledo  1 , Paul M Coen  1   2 , Bret H Goodpaster  1   2
Affiliations

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity

Elizaveta V Menshikova et al. J Gerontol A Biol Sci Med Sci. .

Abstract

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.

Conclusion: 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.

Keywords: Caloric restriction; Glucose uptake; Human aging; Muscle metabolism; Obesity.

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Figures

Figure 1.
Figure 1.
Effect of exercise or calorie restriction interventions on skeletal muscle insulin sensitivity in older sedentary individuals. Glucose clamps were performed before (pre) and after the interventions (post). Data represent Mean ± SEM. *p < .05, Significant within-group differences between pre- and post-intervention. Rd = Rate of disappearance of glucose; FFM = Fat free mass.
Figure 2.
Figure 2.
Effect of exercise or calorie restriction interventions on mitochondrial volume density (A) or cardiolipin content (marker of mitochondrial mass) (B) in skeletal muscle biopsy from older sedentary individuals. Biopsies were analyzed before (pre) and after the interventions (post). Cardiolipin content was normalized to creatine kinase (CK) activity to control for muscle fiber content. Data represent Mean ± SEM. *p < .05, Significant within-group differences between pre- and post-intervention.
Figure 3.
Figure 3.
Effect of exercise or calorie restriction interventions on markers of mitochondrial mass and electron transport chain activity in skeletal muscle biopsy from older sedentary individuals. Biopsies were analyzed before (pre) and after the interventions (post). The total activities of β-HAD (A), citrate synthase (B), and rotenone-sensitive- Nicotinamide adenine dinucleotide (NADH) oxidase (C) in biopsies were normalized to the creatine kinase (CK) activity. Citrate Synthase, β-HAD, and NADH:O2 oxidoreductase activities were normalized to CK activity to control for muscle fiber content. Data represent Mean ± SEM. φp < .05, Significant time effect. *p < .05, Significant within-group differences between pre- and post-intervention. **p < .05, Significant between-group difference at the pre-intervention time point.
Figure 4.
Figure 4.
Ratios between activity of mitochondrial electron transport chain (Nicotinamide adenine dinucleotide; NADH-oxidase), β-oxidation (β-HAD), and tricarboxylic acid (TCA) cycle (Citrate Synthase; CS) in skeletal muscle before (pre) and after (post) the exercise and calorie restriction interventions. Total NADH-oxidase (A) or β-HAD (B) activities in biopsy were normalized to CS activity to examine changes in the relative capacity for mitochondrial electron transport chain/TCA or β-oxidation/TCA. Data represent Mean ± SEM. *p < .05, Significant within-group differences between pre- and post-intervention.
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