Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes

Am J Physiol Regul Integr Comp Physiol. 2005 May;288(5):R1220-5. doi: 10.1152/ajpregu.00397.2004. Epub 2004 Dec 16.


Obesity and insulin resistance are often associated with lower circulating adiponectin concentrations and elevated serum interleukin-6 (IL-6) and/or tumor necrosis factor-alpha (TNF-alpha). Adiponectin suppresses activation of nuclear factor-kappaB (NF-kappaB) in aortic endothelial cells and porcine macrophages. Accordingly, we hypothesized that adiponectin is an anti-inflammatory hormone and suppresses activation of NF-kappaB in adipocytes. Because peroxisome proliferator-activated receptor gamma2 (PPARgamma2) antagonizes the transcriptional activity of NF-kappaB, we determined whether adiponectin alters PPARgamma2 expression in pig adipocytes. In addition, we determined whether interferon-gamma alters the expression of PPARgamma2 in the presence or absence of adiponectin. Primary adipocytes from pig subcutaneous adipose tissue were treated with or without lipopolysaccharide (LPS; 10 microg/ml) and adiponectin (30 microg/ml), and nuclear extracts were obtained for gel shift assays to assess nuclear localization of NF-kappaB. Whereas LPS induced an increase in NF-kappaB activation, adiponectin suppressed both NF-kappaB activation and the induction of IL-6 expression by LPS (P<0.05). Similar results were obtained in 3T3-L1 adipocytes. In addition, adiponectin antagonized LPS-induced increase in TNF-alpha mRNA expression (P<0.05) and tended (P<0.065) to diminish its accumulation in the culture media in 3T3-L1 adipocytes. Adiponectin also induced an upregulation of PPARgamma2 mRNA (P<0.05). Although IFN-gamma did not reduce the basal expression of PPARgamma2, it suppressed PPARgamma2 induction by adiponectin (P<0.05). These findings indicate that adiponectin may be a local regulator of inflammation in the adipocyte and adipose tissue via its regulation of the NF-kappaB and PPARgamma2 transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adiponectin
  • Animals
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Interferon-gamma / physiology
  • Interleukin-6 / biosynthesis*
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / pharmacology
  • Male
  • NF-kappa B / physiology*
  • PPAR gamma / biosynthesis*
  • Swine
  • Up-Regulation


  • Adiponectin
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • PPAR gamma
  • Interferon-gamma