title: Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men.
abstract: 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.
  
  
  METHODS
  Change in gene expression, mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content, and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) 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-1α after overfeeding. Interestingly, this reduction of the sirtuin PGC-1α pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions.
  
  
  CONCLUSIONS
  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-1α 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.
authors.affiliation: INSERM Unité Mixte de Recherche 1060 (K.S., M.A., E.M., E.L., E.D., E.B., J.R., M.L., H.V.), Laboratoires CarMeN et Centre Européen pour la Nutrition et la Santé, Université Lyon 1, F-69600 Oullins, France; Centre de Recherche en Nutrition Humaine Rhône-Alpes (K.S., M.A., E.D., S.L.-P., E.B., M.L., H.V.), Centre Hospitalier Lyon-Sud, F-69310 Pierre Bénite, France; Institut National de la Recherche Agronomique Unité 1235 (E.M., J.R., M.L., H.V.), F-69600 Oullins, France; Institut National de la Recherche Agronomique Unité Mixte de Recherche 1019 (E.C., B.M.), Unité de Nutrition Humaine and Centre de Recherche en Nutrition Humaine Auvergne, Université d'Auvergne, F-63000 Clermont-Ferrand, France; Laboratory of Integrative and Systems Physiology (C.C.), Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences - Institute of Bioengineering, CH-1015 Lausanne, Switzerland; and Genfit (J.B.), F-59120 Loos, France.
authors.forename: K
authors.initials: K
authors.lastname: Seyssel
authors.forename: M
authors.initials: M
authors.lastname: Alligier
authors.forename: E
authors.initials: E
authors.lastname: Meugnier
authors.forename: E
authors.initials: E
authors.lastname: Chanseaume
authors.forename: E
authors.initials: E
authors.lastname: Loizon
authors.forename: C
authors.initials: C
authors.lastname: Canto
authors.forename: E
authors.initials: E
authors.lastname: Disse
authors.forename: S
authors.initials: S
authors.lastname: Lambert-Porcheron
authors.forename: J
authors.initials: J
authors.lastname: Brozek
authors.forename: E
authors.initials: E
authors.lastname: Blond
authors.forename: J
authors.initials: J
authors.lastname: Rieusset
authors.forename: B
authors.initials: B
authors.lastname: Morio
authors.forename: M
authors.initials: M
authors.lastname: Laville
authors.forename: H
authors.initials: H
authors.lastname: Vidal
mesh_terms: D000328:Adult; D019069:Cell Respiration / Q000187:drug effects / Q000235:genetics; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D044343:Overnutrition / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D004041:Dietary Fats