title: High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator.
abstract: OBJECTIVE
  To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ.
  
  
  METHODS
  Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation.
  
  
  RESULTS
  The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size.
  
  
  CONCLUSIONS
  These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
authors.affiliation: The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
authors.forename: Victoria Rotter
authors.initials: VR
authors.lastname: Sopasakis
authors.forename: Madeléne
authors.initials: M
authors.lastname: Sandqvist
authors.forename: Birgit
authors.initials: B
authors.lastname: Gustafson
authors.forename: Ann
authors.initials: A
authors.lastname: Hammarstedt
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yang
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
mesh_terms: D000005:Abdomen; D017667:Adipocytes / Q000166:cytology*; D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry / Q000502:physiology*; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D048429:Cell Size; D005269:Femur; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors