2013 Fiscal Year Final Research Report
The beneficial role of vaspin in metabolic syndrome by amelioration of ER stress
Project/Area Number |
24790926
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Metabolomics
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Research Institution | Okayama University |
Principal Investigator |
NAKATSUKA Atsuko 岡山大学, 医歯(薬)学総合研究科, 助教 (00625949)
|
Project Period (FY) |
2012-04-01 – 2014-03-31
|
Keywords | メタボリックシンドローム / インスリン抵抗性 / 動脈硬化 / 小胞体ストレス / アポトーシス / アディポカイン |
Research Abstract |
To study the role of vaspin, we generated vaspin transgenic (Tg) mice and vaspin knockout (KO) mice. Under high fat-high sucrose diet, the obesity, insulin resistance and fatty liver were ameliorated in Tg mice, while they were exacerbated in KO mice. We identified GRP78 as a vaspin-interacting molecule, and GRP78 forms complex with anchor proteins on the plasma membrane. On hepatocytes, vaspin interacts with GRP78/MTJ-1 complex and enhance the phosphorylation of Akt and AMPK, and improves glucose and lipid metabolism. Next, we studied the role of vaspin on atherosclerosis. Vaspin inhibited arterial intimal thickening of balloon injured and cuff-injured vessels of rodent model. Vaspin binds to GRP78/VDAC complex on vascular endothelial cells and competes with the known VDAC ligand, kringle 5. Vaspin inhibits kringle 5-induced apoptosis pathway and enhances the phosphorylation of Akt. Subsequently, vaspin inhibits apoptosis of vascular endothelial cells.
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Research Products
(18 results)