The effects of adiponectin on interleukin-6 and MCP-1 secretion in lipopolysaccharide-treated 3T3-L1 adipocytes: Role of the NF-κB pathway

It was recently suggested that the transcription nuclear factor-kappa B (NF-kappa B) 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-kappa B 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 mu g/ml lipopolysaccharides (LPS) for 16 h, with or without pretreatment with 10 mu g/ml of globular (AdG) or full-length (AdF1) adiponectin. Both AdG and AdF1 significantly suppressed LPS-induced expression of IL-6 rnRNA 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 AdF1 reduced NF-kappa B activity by 50 and 40%, respectively compared to the NF-kappa B activation induced by LPS alone. Moreover, both forms of adiponectin significantly attenuated I kappa B-alpha as well as IKK gene expression. Pre-treatment of adipocytes with AdG or AdF1 significantly increased PPAR gamma mRNA levels, taking its expression back to the basal level. Both AdG and AdF1 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-kappa B activity as well as through increased PPAR gamma expression.