Globular adiponectin upregulates nitric oxide production in vascular endothelial cells.
OBJECTIVE
Adiponectin, also called ACRP30, is a novel adipose tissue-specific protein that has been shown to improve insulin sensitivity and to exert anti-atherogenic effects. It is known that knockout mice lacking endothelial NO synthase (eNOS) develop hypertension, insulin resistance, hyperlipidaemia, and show augmented ischaemia-reperfusion damage. Thus, we examined whether globular adiponectin activates eNOS to produce NO.


METHODS
To analyze NO production in bovine aortic endothelial cells (BAE), NOx (nitrite and nitrate) was measured in the medium with an automated NO detector/high-performance liquid chromatography system. eNOS activation was assessed by phosphorylation of the enzyme and its activity was evaluated by citrulline synthesis in human umbilical vein endothelial cells (HUVEC). eNOS mRNA and protein expressions in HUVEC were evaluated by Realtime PCR and Western blot analysis.


RESULTS
Gobular adiponectin increased NO production in BAE. It also caused eNOS phosphorylation and potentiated eNOS activity in HUVEC. In addition, globular adiponectin up-regulated the eNOS gene to increase protein expression in HUVEC.


CONCLUSIONS
Globular adiponectin increases NO production through two mechanisms, namely, by activation of eNOS enzyme activity and via an increase in eNOS expression. Activation and up-regulation of eNOS could explain some of the observed vasoprotective properties of globular adiponectin, as well as its beneficial effects on the cardiovascular system.
Hattori
Y
Y
Departments of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. yhattori@dokkyomed.ac.jp
Suzuki
M
M
Hattori
S
S
Kasai
K
K
D052242:Adiponectin; D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014471:Umbilical Veins
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III