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

• 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.

Nyckelord

Abdomen

Adipocytes/*cytology

Adiponectin

Adipose Tissue/chemistry/*physiology

Adult

Cell Differentiation/*drug effects/genetics

Cell Size

Femur

Gene Expression/drug effects

Humans

*Intercellular Signaling Peptides and Proteins

Interleukin-6/genetics/pharmacology/*physiology

Male

Microdialysis

Middle Aged

Proteins/genetics

Receptors

Cytoplasmic and Nuclear/genetics

Transcription Factors/genetics

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