Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue

PLoS One. 2014 Jan 8;9(1):e84910. doi: 10.1371/journal.pone.0084910. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cold Temperature*
  • Gene Expression Regulation*
  • Interleukin-6 / blood*
  • Ion Channels / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / genetics*
  • Organ Specificity
  • Phosphorylation
  • Physical Conditioning, Animal*
  • STAT3 Transcription Factor / metabolism
  • Subcutaneous Fat / metabolism*
  • Uncoupling Protein 1


  • Interleukin-6
  • Ion Channels
  • Mitochondrial Proteins
  • STAT3 Transcription Factor
  • Ucp1 protein, mouse
  • Uncoupling Protein 1

Grant support

The study was supported by grants from the Novo Nordisk Foundation, the Lundbeck Foundation, The Danish Research Foundation, The Danish Council for Independent Research in the Natural Sciences, the Augustinus Foundation, the National Health and Medical Research Council of Australia (NHMRC grant no. 526606) and the EU FP7 project DIABAT (HEALTH-F2-2011-278373). Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (#02-512-55). CIM is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology and Innovation. Mark A. Febbraio and Bronwyn A. Kingwell are Senior Principal Research Fellows of the NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.