Elucidation of the mechanism of metabolic syndrome due to the gene targeting analysis of the causative gene

• Project/Area Number: 23591300
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: IIZUKA Yoko 東京大学, 医学部附属病院, 助教 (40420244)
• Co-Investigator(Kenkyū-buntansha): YAHAGI Naoya 筑波大学, 医学医療系, 准教授 (60420246)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: メタボリックシンドローム / インスリン抵抗性 / 高血圧 / 交感神経活動亢進 / 原因候補遺伝子 / 高血圧自然発症ラットSHR / ノックアウトマウス / 尿崩症 / 肥満

Research Abstract

[Purpose and methods] Through the gene targeting analysis of KAT-1, I explore the origin of metabolic syndrome and its physiological function. [Results and conclusions] As with the SHR, KAT-1 knockout mice exhibited an increase in blood pressure and heart rate significant in a normal diet and 12 weeks high salt diet, exhibited enhanced catecholamine secretion of 24-hour urine in high salt diet, showed an increase in plasma aldosterone concentration and a decreased in renin activity, showed a significant increase in fasting blood glucose levels and the enhancement of insulin resistance by insulin tolerance test in normal diet. Along with the increase in activity, and showed a decrease in the rate of increase in body weight, adipose tissue weight in the high-fat diet. It was strongly suggested that KAT-1 is a potential new therapeutic targets for metabolic syndrome.

Research Products

• [Presentation] SHRのメタボリックシンドローム原因候補遺伝子(KAT-1)の欠損マウスを用いた生理的機能の解明 (2011)
  • Author(s): 飯塚陽子,大須賀淳一,喬荊,武内謙憲,高瀬暁,高梨幹生,西真貴子,久保田みどり,升田紫,熊谷真義,太田啓介,山本隆史,泉田欣彦,矢作直也,大橋健,島野仁,石橋俊,藤田敏郎,山田信博,後藤田貴也,門脇孝
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] SHRのメタボリックシンドローム原因候補遺伝子(KAT-1)欠損マウスを用いたその生理的機能の解明 (2011)
  • Author(s): 飯塚陽子,喬荊,大須賀淳一,武内謙憲,高瀬暁,高梨幹生,西真貴子,久保田みどり,升田紫,熊谷真義,太田啓介,山本隆史,泉田欣彦,矢作直也,大橋健,島野仁,石橋俊,藤田敏郎,山田信博,後藤田貴也,門脇孝
  • Organizer: 第26回日本糖尿病合併症学会
  • Place of Presentation: 大宮
• [Presentation] SHRのメタボリックシンドローム原因候補遺伝子（KAT-1）欠損マウスを用いたその生理的機能の解明 (2011)
  • Author(s): 飯塚 陽子、他
  • Organizer: 第26回日本糖尿病合併症学会
  • Place of Presentation: 大宮