Impact of obesity-induced dysregulation of renin-angiotensin-aldosterone system in the hypothalamus on the homeostasis of energy metabolism.

肥胖引起的下丘脑肾素-血管紧张素-醛固酮系统失调对能量代谢稳态的影响。

• 批准号: 22790852
• 负责人: WADA Tsutomu
• 金额: $ 2.58万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790852/
• 关键词: 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

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.

血管紧张素（AT2）刺激了通过AT2的ROS产物的胰岛素胰岛素抵抗的ROS产生。肝脏在假设中的促炎细胞因子的表达升高。 MRA，但没有有效地改善增强的生产。

项目成果

エストロゲンの中枢及び末梢投与が全身のエネルギーバランス、体脂肪分布と糖・脂質代謝に与える影響

中枢和外周雌激素给药对全身能量平衡、体脂肪分布和糖脂代谢的影响

• 发表时间: 2011
• 作者: 坂本英里子;尾崎信暁;清野祐介;深見亜也子;佐藤寛之;原田憲雄;水谷直広;豊田行康;三輪一智;稲垣暢也;大磯ユタカ;坂本英里子;米澤理可,和田努,森田真裕子,恒枝宏史,笹岡利安,斎藤滋
• 通讯作者: 米澤理可,和田努,森田真裕子,恒枝宏史,笹岡利安,斎藤滋

新規NASHモデルマウスの作成と、抗アルドステロン薬の治療効果の検討

新型NASH模型小鼠的制作及抗醛固酮药物的治疗效果检验

• 发表时间: 2011
• 作者: Wada T.;Tsuneki H.;Sasaoka T.;坂本英里子;佐々木元大,和田努,宮下佑介,石井陽子,笹原正清,恒枝宏史,笹岡利安
• 通讯作者: 佐々木元大,和田努,宮下佑介,石井陽子,笹原正清,恒枝宏史,笹岡利安

Antagonism of mineralocorticoid receptor ameliorates systemic insulin resistance and steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis (NASH) utilizing liver-specific SREBP1c transgenic mice.

在利用肝脏特异性 SREBP1c 转基因小鼠的新型非酒精性脂肪性肝炎 (NASH) 小鼠模型中，盐皮质激素受体的拮抗作用可改善全身胰岛素抵抗和脂肪性肝炎。

• 发表时间: 2011
• 作者: T.Wada;Y.Miyashita;M.Sasaki;Y.Ishii;M.Sasahara;H.Tsuneki;T.Sasaoka
• 通讯作者: T.Sasaoka

Spironolactone Improves Glucose and Lipid Metabolism by Ameliorating Hepatic Steatosis and Inflammation and Suppressing Enhanced Gluconeogenesis Induced by High-Fat and High-Fructose Diet

• DOI: 10.1210/en.2009-0869
• 发表时间: 2010-05-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Wada, Tsutomu;Kenmochi, Hiroki;Sasaoka, Toshiyasu
• 通讯作者: Sasaoka, Toshiyasu

Blockade of mineralocorticoid receptor improves insulin resistance and steatohepatitis in a novel mouse model of non-alchoholic steatohepatitis(NASH) utilizing liver-specific SREBP1c transgenic mice

利用肝脏特异性 SREBP1c 转基因小鼠，阻断盐皮质激素受体可改善新型非酒精性脂肪性肝炎 (NASH) 小鼠模型中的胰岛素抵抗和脂肪性肝炎

• 发表时间: 2011
• 作者: Sasaoka T.;Miyashita Y.;Sasaki M.;Tsuneki H.;Wada T.
• 通讯作者: Wada T.