1. Adiponectin inhibits LPS-induced NF-κB activation and IL-6 production and increases PPARγ2 expression in adipocytes.
- Author
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Ajuwon, Kolapo M. and Spurlock, Michael E.
- Subjects
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FAT cells , *HORMONES , *BIOMOLECULES , *TRANSCRIPTION factors , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Obesity and insulin resistance are often associated with lower circulating adiponectin concentrations and elevated serum interleukin-6 (IL-6) and/or tumor necrosis factor-a (TNF-α). Adiponectin suppresses activation of nuclear factor-κB (NF-κB) in aortic endothelial cells and porcine macrophages. Accordingly, we hypothesized that adiponectin is an anti-inflammatory hormone and suppresses activation of NF-κB in adipocytes. Because peroxisome proliferator-activated receptor γ2 (PPARγ2) antagonizes the transcriptional activity of NF-κB, we determined whether adiponectin alters PPARγ2 expression in pig adipocytes. In addition, we determined whether interferon-γ alters the expression of PPARγ2 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-κB. Whereas LPS induced an increase in NF-κB activation, adiponectin suppressed both NF-κB 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-α 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 PPARγ2 mRNA (P < 0.05). Although IFN-γ did not reduce the basal expression of PPARγ2, it suppressed PPARγ2 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-κB and PPARγ2 transcription factors. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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