title: Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis.
abstract: BACKGROUND
  Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupling in skeletal muscle has not extensively been studied in relation to adaptive thermogenesis in humans. Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is accompanied by an increase in mitochondrial uncoupling in skeletal muscle.
  
  
  RESULTS
  The metabolic response to mild cold exposure in 11 lean, male subjects was measured in a respiration chamber at baseline and mild cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in muscle biopsies taken at the end of the respiration chamber stays. Mild cold exposure caused a significant increase in 24h energy expenditure of 2.8% (0.32 MJ/day, range of -0.21 to 1.66 MJ/day, p<0.05). The individual increases in energy expenditure correlated to state 4 respiration (p<0.02, R(2) = 0.50).
  
  
  CONCLUSIONS
  This study for the first time shows that in humans, skeletal muscle has the intrinsic capacity for cold induced adaptive thermogenesis via mitochondrial uncoupling under physiological conditions. This opens possibilities for mitochondrial uncoupling as an alternative therapeutic target in the treatment of obesity.
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, The Netherlands. S.Wijers@hb.unimaas.nl
authors.forename: Sander L J
authors.initials: SL
authors.lastname: Wijers
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Wouter D
authors.initials: WD
authors.lastname: van Marken Lichtenbelt
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D004734:Energy Metabolism; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology