Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men

K. Seyssel , M. Alligier , E. Meugnier , E. Chanseaume , E. Loizon , C. Canto , Emmanuel Disse (1) , S. Lambert-Porcheron , J. Brozek , Eric Blond , J. Rieusset , Béatrice Morio (1) , M. Laville (1) , Hubert Vidal (1)

1 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

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-1alpha (PGC-1alpha) 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-1alpha after overfeeding. Interestingly, this reduction of the sirtuin PGC-1alpha 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-1alpha 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.

Mots clés: Diet; High-Fat; Dietary Fats/*administration & dosage; Oxidation-Reduction; *Energy Metabolism/drug effects/genetics; Cell Respiration/drug effects/genetics; Mitochondria; Muscle/drug effects/*physiology; Muscle; Skeletal/drug effects/*metabolism; Overnutrition/genetics/*metabolism; Male; Adult; Humans; Lipid Metabolism/drug effects/genetics

Domaines: Sciences du Vivant [q-bio]

K. Seyssel, M. Alligier, E. Meugnier, E. Chanseaume, E. Loizon, et al.. Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men. Journal of Clinical Endocrinology and Metabolism, 2014, 99 (7), pp.E1254-62. ⟨10.1210/jc.2013-4379⟩. ⟨hal-01859423⟩