title: Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue.
abstract: Expression of brown adipose tissue (BAT) associated proteins like uncoupling protein 1 (UCP1) in inguinal WAT (iWAT) has been suggested to alter iWAT metabolism. The aim of this study was to investigate the role of interleukin-6 (IL-6) in exercise training and cold exposure-induced iWAT UCP1 expression. The effect of daily intraperitoneal injections of IL-6 (3 ng/g) in C57BL/6 mice for 7 days on iWAT UCP1 expression was examined. In addition, the expression of UCP1 in iWAT was determined in response to 3 days of cold exposure (4°C) and 5 weeks of exercise training in wild type (WT) and whole body IL-6 knockout (KO) mice. Repeated injections of IL-6 in C57BL/6 mice increased UCP1 mRNA but not UCP1 protein content in iWAT. Cold exposure increased iWAT UCP1 mRNA content similarly in IL-6 KO and WT mice, while exercise training increased iWAT UCP1 mRNA in WT mice but not in IL-6 KO mice. Additionally, a cold exposure-induced increase in iWAT UCP1 protein content was blunted in IL-6 KO mice, while UCP1 protein content in iWAT was lower in both untrained and exercise trained IL-6 KO mice than in WT mice. In conclusion, repeated daily increases in plasma IL-6 can increase iWAT UCP1 mRNA content and IL-6 is required for an exercise training-induced increase in iWAT UCP1 mRNA content. In addition IL-6 is required for a full induction of UCP1 protein expression in response to cold exposure and influences the UCP1 protein content iWAT of both untrained and exercise trained animals.
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jakob G
authors.initials: JG
authors.lastname: Knudsen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark ; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Murholm
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Carey
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus S
authors.initials: RS
authors.lastname: Biensø
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark ; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Astrid L
authors.initials: AL
authors.lastname: Basse
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Allen
authors.affiliation: Department of Neuroscience, Universidad Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
mesh_terms: D000818:Animals; D003080:Cold Temperature; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000097:blood*; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics*; D009928:Organ Specificity; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*; D000071256:Uncoupling Protein 1
chemical_list: D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D050796:STAT3 Transcription Factor; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1