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Am J Physiol Regul Integr Comp Physiol 288: R1220-R1225, 2005. First published December 16, 2004; doi:10.1152/ajpregu.00397.2004
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Adiponectin inhibits LPS-induced NF-{kappa}B activation and IL-6 production and increases PPAR{gamma}2 expression in adipocytes

Kolapo M. Ajuwon and Michael E. Spurlock

Department of Animal Sciences, Comparative Medicine Center, Purdue University, West Lafayette, Indiana

Submitted 14 June 2004 ; accepted in final form 15 December 2004

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-{kappa}B (NF-{kappa}B) in aortic endothelial cells and porcine macrophages. Accordingly, we hypothesized that adiponectin is an anti-inflammatory hormone and suppresses activation of NF-{kappa}B in adipocytes. Because peroxisome proliferator-activated receptor {gamma}2 (PPAR{gamma}2) antagonizes the transcriptional activity of NF-{kappa}B, we determined whether adiponectin alters PPAR{gamma}2 expression in pig adipocytes. In addition, we determined whether interferon-{gamma} alters the expression of PPAR{gamma}2 in the presence or absence of adiponectin. Primary adipocytes from pig subcutaneous adipose tissue were treated with or without lipopolysaccharide (LPS; 10 µg/ml) and adiponectin (30 µg/ml), and nuclear extracts were obtained for gel shift assays to assess nuclear localization of NF-{kappa}B. Whereas LPS induced an increase in NF-{kappa}B activation, adiponectin suppressed both NF-{kappa}B 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 PPAR{gamma}2 mRNA (P < 0.05). Although IFN-{gamma} did not reduce the basal expression of PPAR{gamma}2, it suppressed PPAR{gamma}2 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-{kappa}B and PPAR{gamma}2 transcription factors.

adipocyte; pig; nuclear factor-{kappa}B; interleukin-6; interferon-{gamma}; peroxisome proliferator-activated receptor {gamma}



Address for reprint requests and other correspondence: M. E. Spurlock, Purdue Univ., 3-230 Lilly Hall of Life Sciences, 915 W State St., West Lafayette, IN 47907-2054 (E-mail: spurloc0{at}purdue.edu)




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