Impact of obesity-induced dysregulation of renin-angiotensin-aldosterone system in the hypothalamus on the homeostasis of energy metabolism.
| Project/Area Number |
22790852
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | University of Toyama |
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Principal Investigator |
WADA Tsutomu 富山大学, 大学院・医学薬学研究部(薬学), 助教 (00419334)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | アルドステロン / 炎症性サイトカイン / 糖尿病 / ROS / ミトコンドリア / 視床下部 / 炎症 / レニン・アンギオテンシン系 |
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| Research Abstract |
Angiotensin2(AT2) stimulates ROS production in peripheral tissues and promotes insulin resistance. We have indicated that aldosterone also induces insulin resistance through ROS production independent of AT2. To demonstrate the in vivo impact of MRA, we administrated mineralocorticoid antagonist(MRA) to the mice model of metabolic syndrome accompanied with steatohepatitis(NASH model). Administration of MRA effectively ameliorated systemic insulin resistance, dyslipidemia, and abnormal histological change in the liver. Diabetic models of both high-fat diet(HFD)-fed mice and db/db mice showed elevated expressions of proinflammatory cytokines in the hypothalamus. However, systemic administration of MRA did not affect these inflammatory changes in the hypothalamus. In bone marrow derived macrophage(BMDM), pretreatment of H2O2 or NAC, a ROS scavenger did not affect LPS-induced TNFαproduction. In addition, pretreatment with MRA, but not ARB effectively ameliorated the enhanced production.
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Report
(3 results)
Research Products
(12 results)
