The effects of adiponectin on interleukin-6 and MCP-1 secretion in lipopolysaccharide-treated 3T3-L1 adipocytes: role of the NF-kappaB pathway.
It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an important role in controlling the inflammation and metabolic alterations associated with obesity. In endothelial and monocytic cells, adiponectin acts as a modulator of the inflammatory response, suppressing NF-kappaB activation. The aim of this study was to assess the ability of different forms of adiponectin to modulate the inflammatory response in adipocytes. 3T3-L1 preadipocytes were cultured according to standard conditions. Fully differentiated adipocytes were stimulated with 1 microg/ml lipopolysaccharides (LPS) for 16 h, with or without pre-treatment with 10 microg/ml of globular (AdG) or full-length (AdFl) adiponectin. Both AdG and AdFl significantly suppressed LPS-induced expression of IL-6 mRNA in adipocytes and reduced the concentration of IL-6 in culture media. Adiponectin pre-treatment significantly reduced the increase in MCP-1 mRNA in adipocytes exposed to LPS. In culture media, the increase in MCP-1 detected after LPS stimulation was significantly attenuated after pre-treatment with AdG. In 3T3-L1, AdG and AdFl reduced NF-kappaB activity by 50 and 40%, respectively compared to the NF-kappaB activation induced by LPS alone. Moreover, both forms of adiponectin significantly attenuated IkappaB-alpha as well as IKK gene expression. Pre-treatment of adipocytes with AdG or AdFl significantly increased PPARgamma mRNA levels, taking its expression back to the basal level. Both AdG and AdFl exert anti-inflammatory activity suppressing IL-6 and MCP-1 production from inflamed adipocytes. This anti-inflammatory action may be mediated through inhibition of NF-kappaB activity as well as through increased PPARgamma expression.
Zoico
Elena
E
Division of Geriatric Medicine, Department of Surgical and Biomedical Sciences, University of Verona, I-37126 Verona, Italy. elena.zoico@univr.it
Garbin
Ulisse
U
Olioso
Debora
D
Mazzali
Gloria
G
Fratta Pasini
Anna Maria
AM
Di Francesco
Vincenzo
V
Sepe
Anna
A
Cominacini
Luciano
L
Zamboni
Mauro
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; C499919:Adipoq protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D011994:Recombinant Proteins