High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-κB activation in vascular endothelial cells

Various isoforms of adiponectin circulate in the plasma. We purified high molecular weight (HMW) adiponectin from human plasma. HMW adiponectin was observed to activate AMP-activated protein kinase (AMPK), thereby increasing the phosphorylation of eNOS and NO production in endothelial cells. On the other hand, cells preincubated with HMW adiponectin had reduced TNFα-induced NF-κB activation. HMW adiponectin by itself was found to modestly activate NF-κB, which was significantly enhanced by inhibition of AMPK/eNOS activation. Thus, HMW adiponectin might have dual action, both pro and anti-inflammatory. An initial period of NF-κB activation by HMW adiponectin might be proinflammatory, but it could be counteracted by activation of AMPK/eNOS, which lead to a potential reduction in a second activation of NF-κB against inflammatory stimuli.