期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 99, 期 7, 页码 E1254-E1262出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2013-4379
关键词
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资金
- Hospices Civils de Lyon
- Programme Hospitalier de Recherche Clinique Interregional
- Agence Nationale de la Recherche (Programme de Recherche en Nutrition Humaine and the Programme National de Recherche en Alimentation)
- Innovation Strategique Industrielle program of the Agence pour l'Innovation OSEO (Innovation Therapeutique - Diabete project)
- Ministere de l'Enseignement Superieur et de la Recherche (France)
Context/Objective: The aim of this study was to evaluate the regulation of the fuel partitioning and energy metabolism in skeletal muscle during lipid overfeeding in healthy men. Design/Participants/Intervention: Thirty-nine healthy volunteers were overfed for 56 days with a high-fat diet (3180 kJ/d). Energy metabolism (indirect calorimetry) was characterized in the fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at day 0 and day 56. Main Outcome Measures: Change in gene expression, mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content, and acetylation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) in skeletal muscle was measured. Results: Overfeeding increased body weight (+2.6 kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel toward preferential oxidation of carbohydrates instead of lipids. Changes in lipid metabolic gene expression supported this observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that could be the consequences of decreased NAD(+) concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1 alpha after overfeeding. Interestingly, this reduction of the sirtuin PGC-1 alpha pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions. Conclusion: Adaptation to lipid overfeeding and regulation of fuel partitioning in human muscle appear to rely on a dissociation between the regulatory functions of the sirtuin-PGC-1 alpha pathway on fatty acid oxidation and on mitochondrial regulation. This may facilitate lipid storage during a period of positive energy balance while maintaining mitochondrial functions and oxidative capacities.
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