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

Abstract

It was recently suggested that the transcription nuclear factor-κB (NF-κB) 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-κB 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 μg/ml lipopolysaccharides (LPS) for 16 h, with or without pre-treatment with 10 μg/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-κB activity by 50 and 40%, respectively compared to the NF-κB activation induced by LPS alone. Moreover, both forms of adiponectin significantly attenuated IκB-α as well as IKK gene expression. Pre-treatment of adipocytes with AdG or AdFl significantly increased PPARγ 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-κB activity as well as through increased PPARγ expression.