High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator

Obes Res. 2004 Mar;12(3):454-60. doi: 10.1038/oby.2004.51.

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.

Research methods and procedures: 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.

Discussion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen
  • Adipocytes / cytology*
  • Adiponectin
  • Adipose Tissue / chemistry
  • Adipose Tissue / physiology*
  • Adult
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Size
  • Femur
  • Gene Expression / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-6 / genetics
  • Interleukin-6 / pharmacology
  • Interleukin-6 / physiology*
  • Male
  • Microdialysis
  • Middle Aged
  • Proteins / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Transcription Factors / genetics

Substances

  • Adiponectin
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors