Research Projects -
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Vaspin and its interacting molecules as therapeutic targets for metabolic syndrome
Grant number：26293218 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Wada Jun, NAKATSUKA Atsuko
Grant amount：\16510000 （ Direct expense: \12700000 、 Indirect expense：\3810000 ）
We identified vaspin (visceral adipose tissue-derived serine protease inhibitor) as a novel adlipokine. Vaspin inhibits insulin resistance, fatty liver, dyslipidemia and atherosclerosis in metabolic syndrome. Vaspin inhibits kallikrein 7 belonging to serine protease and increases glucagon-like peptide-1. We generated DNAJC1 (DnaJ homolog, subfamily C, member 1) conditional knockout mice and we demonstrated that they are therapeutic targets for metabolic syndrome.
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The role of vaspin in metabolic syndrome associated renal disease
Grant number：26461361 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Nakatsuka Atsuko, WADA Jun
Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）
We previously identified an adipokine, vaspin. In this study, we checked the beneficial role of vaspin in renal injury of metabolic syndrome. Vaspin transgenic(Tg) and vaspin-/- mice were fed with high fat high sucrose (HFHS) diet. At 30 weeks of age, prominent vacuolation in the kidney tissues of vaspin-/- mice under HFHS diet are observed, and it is meliorated in Tg mice. These vacuoles are toluidine blue positive and EM demonstrates lysosomal enlargement. TUNEL-positive apoptotic tubular cells increase in vaspin-/- mice fed with HFHS compared with Tg and wild type mice. Next, we investigated the streptozotocin(STZ) induced-diabetes model. In Tg mice, the dilatation and thinning of tubules induced by diabetes are ameliorated. TUNEL-positive apoptotic cells are increased in STZ induced diabetic vaspin-/- mice, while in Tg mice apoptosis was inhibited. It is suspected that vaspin ameliorate tubulointerstitial injury in diabetic and metabolic syndrome associated renal disease.
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Grant number：26461362 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Murakami Kazutoshi, WADA JUN, EGUCHI JUN, NAKATSUKA ATSUKO
Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）
The excess of lipid accumulation and hypertrophy of adipocytes induces the abnormality of secretion of adipokines and hormones from adipocytes and causes metabolic syndrome and diabetes. We identified ACAM in 2005 from the visceral fat tissue of obese rats. It is a cell adhesion molecule responsible for the homophilic adhesion of the cells. In the transgemic mice overexpressing ACAM in adipocytes fed with a high fat and high sucrose diet were protected from the onset of obesity and diabetes. In transgemnic mice, ACAM is abundantly expressed on plasma membrane of mature adipocytes and associated with formation of Phalloidin-positive polymerized form of cortical actin (F-actin). By electron microscopy, the structure of zonula adherens was formed at interphase of adipocytes. The adhesion of adipocytes and formation of cortical actin prevent the adipocyte hypertrophy and development of obesity and diabetes.
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Pemt欠損による肝細胞アポトーシス遷延と脂肪肝炎進展機構の解明
2014
公益財団法人山陽放送学術文化財団 第52回（平成26年度）学術奨励賞
Authorship：Principal investigator
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脂肪肝炎における肝再生機構に寄与する脂肪酸の同定
2014
公益財団法人ウイルス肝炎研究財団 平成26年度研究奨励金
Authorship：Principal investigator
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VaspinのGLP-1を介した血糖調節機構の解明
2014
公益財団法人日本糖尿病財団 第4回(平成26年度)リリー・インクレチン基礎研究助成金
Authorship：Principal investigator
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第73回アメリカ糖尿病学会参加・発表, PEMTのメタボリックシンドロームにおける意義の解明
2013
公益財団法人ウエスコ学術振興財団 平成25年度学術研究費助成金（海外渡航費助成）
Authorship：Principal investigator
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糖尿病細小血管障害におけるVaspinの意義
2013
公益財団法人万有生命科学振興国際交流財団 Banyu Foundation Research Grant 2013
Authorship：Principal investigator
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Vaspinによる小胞体ストレス制御と糖尿病性腎症治療薬の開発
2013
公益財団法人 宇部興産学術振興財団 第53回学術研究費援助金（渡辺記念特別奨励賞）
Authorship：Principal investigator
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VDAC/GRP78経路を介した血管内皮細胞アポトーシスの制御
2013
公益財団法人成人血管病研究振興財団 平成25年度岡本研究奨励賞
Authorship：Principal investigator
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The beneficial role of vaspin in metabolic syndrome by amelioration of ER stress
Grant number：24790926 2012.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
NAKATSUKA Atsuko
Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）
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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Vaspinと血管内皮細胞機能
2012
公益財団法人上原記念生命科学財団 研究奨励金
Authorship：Principal investigator
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Vaspinによる動脈硬化抑制とその作用機序の解明
2012
公益財団法人日本心臓財団 日本心臓財団・アステラス・ファイザー「動脈硬化」Update研究助成
Authorship：Principal investigator