Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes.
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.
Ajuwon
Kolapo M
KM
Department of Animal Sciences, Comparative Medicine Center, Purdue Univ., 3-230 Lilly Hall of Life Sciences, 915 W State St., West Lafayette, IN 47907-2054, USA.
Spurlock
Michael E
ME
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D047495:PPAR gamma / Q000096:biosynthesis*; D013552:Swine; D015854:Up-Regulation
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D007371:Interferon-gamma