title: High levels of whole-body energy expenditure are associated with a lower coupling of skeletal muscle mitochondria in C57Bl/6 mice.
abstract: Considerable variation in energy expenditure is observed in C57Bl/6 mice on a high-fat diet. Because muscle tissue is a major determinant of whole-body energy expenditure, we set out to determine the variation in energy expenditure and its possible association with skeletal muscle mitochondrial function upon high-fat diet intervention. Metabolic cages using indirect calorimetry were used to assess whole-body energy metabolism in C57Bl/6 male mice during the first 3 days of high-fat diet intervention. Mice were grouped in a negative or positive residual nocturnal energy expenditure group after correction of total nocturnal energy expenditure for body mass by residual analysis. The positive residual energy expenditure group was characterized by higher uncorrected total nocturnal energy expenditure and food intake. On day 7, mitochondria were isolated from the skeletal muscle of the hind limb. Mitochondrial density was determined by mitochondrial protein content and did not differ between the positive and negative residual energy expenditure groups. Using high-resolution respirometry, mitochondrial oxidative function was assessed using various substrates. Mitochondria from the positive residual energy expenditure group were characterized by a lower adenosine diphosphate-stimulated respiration and lower respiratory control rates using palmitoyl-coenzyme A as substrate. These results indicate that reduced mitochondrial coupling is associated with positive residual energy expenditure and high rates of total energy expenditure in vivo.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands. svdberg@lumc.nl
authors.forename: Sjoerd A A
authors.initials: SA
authors.lastname: van den Berg
authors.forename: Miranda
authors.initials: M
authors.lastname: Nabben
authors.forename: Silvia
authors.initials: S
authors.lastname: Bijland
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Jan Bert
authors.initials: JB
authors.lastname: van Klinken
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
authors.forename: Matthijs K
authors.initials: MK
authors.lastname: Hesselink
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
mesh_terms: D000818:Animals; D002153:Calorimetry, Indirect / Q000379:methods*; D019069:Cell Respiration; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004041:Dietary Fats; D024101:Mitochondrial Proteins