title: High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-kappaB activation in vascular endothelial cells.
abstract: 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 TNFalpha-induced NF-kappaB activation. HMW adiponectin by itself was found to modestly activate NF-kappaB, 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-kappaB 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-kappaB against inflammatory stimuli.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. yhattori@dokkoymed.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hattori
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tomizawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.forename: Kiuo
authors.initials: K
authors.lastname: Kasai
mesh_terms: D055372:AMP-Activated Protein Kinases; D052242:Adiponectin / Q000494:pharmacology*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology / Q000502:physiology; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D007527:Isoenzymes; D009097:Multienzyme Complexes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases