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Impact of prolonged overfeeding on skeletal muscle mitochondria in healthy individuals.

ABSTRACT: AIMS/HYPOTHESES:Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function. METHODS:Twenty-six healthy volunteers (21 men, 5 women, age 25.3 ± 4.5 years, BMI 25.5 ± 2.4 kg/m2) underwent a supervised protocol consisting of 8 weeks of high-fat overfeeding (40% over baseline energy requirements). Before and after overfeeding, we measured systemic fuel oxidation by indirect calorimetry and performed skeletal muscle biopsies to measure mitochondrial gene expression, content and function in vitro. Mitochondrial function in vivo was measured by 31P NMR spectroscopy. RESULTS:With overfeeding, volunteers gained 7.7 ± 1.8 kg (% change 9.8 ± 2.3). Overfeeding increased fasting NEFA, LDL-cholesterol and insulin concentrations. Indirect calorimetry showed a shift towards greater reliance on lipid oxidation. In skeletal muscle tissue, overfeeding increased ceramide content, lipid droplet content and perilipin-2 mRNA expression. Phosphorylation of AMP-activated protein kinase was decreased. Overfeeding increased mRNA expression of certain genes coding for mitochondrial proteins (CS, OGDH, CPT1B, UCP3, ANT1). Despite the stress of nutrient overload, mitochondrial content and mitochondrial respiration in muscle did not change after overfeeding. Similarly, overfeeding had no effect on either the emission of reactive oxygen species or on mitochondrial function in vivo. CONCLUSIONS/INTERPRETATION:Skeletal muscle mitochondria are significantly resilient to nutrient overload. The lower skeletal muscle mitochondrial oxidative capacity in human obesity is likely to be caused by reasons other than nutrient overload per se. TRIAL REGISTRATION:ClinicalTrials.gov NCT01672632.

SUBMITTER: Toledo FGS

PROVIDER: S-EPMC5770194 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Impact of prolonged overfeeding on skeletal muscle mitochondria in healthy individuals.

Toledo Frederico G S FGS Johannsen Darcy L DL Covington Jeffrey D JD Bajpeyi Sudip S Goodpaster Bret B Conley Kevin E KE Ravussin Eric E

Diabetologia 20171117 2

<h4>Aims/hypotheses</h4>Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function.<h4>Methods</h4>Twenty-six healthy volunteers (21 men, 5 women, age 25.3 ± 4. ...[more]

PMID: 29150696

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Project description:BackgroundThe associations between long-term changes in body mass composition and decline in lung function in healthy adults are unknown.MethodsUsing a well-defined health check-up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m)2 ] or FM index (FMI) [FM (kg)/height (m)2 ] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups.ResultsA total of 15 476 middle-aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5-9) over an average follow-up period of 8.95 years (IQR: 6.73-11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m2 in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m2 in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss).ConclusionsChange in body composition over time can be used to identify healthy middle-aged individuals at high risk for rapid FEV1 decline.

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Impact of prolonged overfeeding on skeletal muscle mitochondria in healthy individuals.

Publications

Impact of prolonged overfeeding on skeletal muscle mitochondria in healthy individuals.

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