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

Research Project

Project/Area Number 22790852
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Metabolomics
Research InstitutionUniversity of Toyama

Principal Investigator

WADA Tsutomu  富山大学, 大学院・医学薬学研究部(薬学), 助教 (00419334)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
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)
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
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.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (12 results)

All 2012 2011 2010

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (10 results)

  • [Journal Article] Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet2012

    • Author(s)
      Wada T, Yonezawa R, Matsumoto N, Morita M, Sawakawa K, Ishii Y, Sasahara M, Tsuneki H, Saito S, Sasaoka T.
    • Journal Title

      Am J Physiol Endocrinol Metab

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet2010

    • Author(s)
      Wada T, Kenmochi H, Miyashita Y, Sasaki M, Ojima M, Sasahara M, Koya D, Tsuneki H, Sasaoka T.
    • Journal Title

      Endocrinology

      Volume: 151 Pages: 2040-2049

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] Blockade of mineralocorticoid receptor improves insulin resistance and steatohepatitis in a novel mouse model of non-alchoholic steatohepatitis(NASH) utilizing liver-specific SREBP1c transgenic mice2011

    • Author(s)
      Sasaoka T., Miyashita Y., Sasaki M., Tsuneki H., Wada T.
    • Organizer
      American Diabetes Association(ADA) 71st Scientific Sessions
    • Place of Presentation
      San Diego, CA, U. S. A
    • Related Report
      2011 Final Research Report
  • [Presentation] Blockade of mineralocorticoid receptor ameliorates glucose metabolism and steatohepatitis in a novel mice model of non-alcoholic steatohepatitis2011

    • Author(s)
      Wada T., Tsuneki H., Sasaoka T.
    • Organizer
      2011 International Conference of Diabetes and Metabolism
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Final Research Report
  • [Presentation] 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2011

    • Author(s)
      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
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 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2011

    • Author(s)
      米澤理可,和田努,森田真裕子,恒枝宏史,笹岡利安,斎藤滋
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Blockade of mineralocorticoid receptor improves insulin resistance and steatohepatitis in a novel mouse model of non-alchoholic steatohepatitis (NASH) utilizing liver-specific SREBP1c transgenic mice2011

    • Author(s)
      Sasaoka T, Miyashita Y, Sasaki M, Tsuneki H, Wada T
    • Organizer
      American Diabetes Association (ADA) 71^<st> Scientific Sessions
    • Place of Presentation
      San Diego, CA, U.S.A.
    • Related Report
      2011 Annual Research Report
  • [Presentation] Blockade of mineralocorticoid receptor ameliorates glucose metabolism and steatohepatitis in a novel mice model of non-alcoholic steatohepatitis2011

    • Author(s)
      Wada T, Tsuneki H, Sasaoka T
    • Organizer
      2011 International Conference of Diabetes and Metabolism
    • Place of Presentation
      Seoul, Korea(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 特異的SREBP1c過剰発現と脂肪・果糖負荷による脂肪性肝炎:アルドステロン阻害薬の効果と創薬2011

    • Author(s)
      笹岡利安, 佐々木元大, 恒枝宏史, 和田努
    • Organizer
      第12回Pharmaco-Hematology Symposium
    • Place of Presentation
      富山
    • Related Report
      2011 Annual Research Report
  • [Presentation] 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.2011

    • Author(s)
      T.Wada, Y.Miyashita, M.Sasaki, Y.Ishii, M.Sasahara, H.Tsuneki, T.Sasaoka
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone CO., USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝特異的SREBP1cトランスジェニックマウスを用いた新規NASHモデルマウスに対する、エプレレノンの改善作用の検討2010

    • Author(s)
      和田努、宮下佑介、佐々木元大、石井陽子、笹原正清、恒枝宏史、笹岡利安
    • Organizer
      第22回分子糖尿病学シンポジウム
    • Place of Presentation
      東京コンファレンスセンター品川
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Blockade of mineralocorticoid receptor ameliorates glucose and lipid metabolism, steatohepatitis, and hepatic fibrosis in a novel mouse model of non-alcoholic steatohepatitis (NASH) utilizing liver-specific SREBP1c transgenic mice.2010

    • Author(s)
      T.Wada, Y.Miyashita, M.Sasaki, Y.Ishii, M.Sasahara, H.Tsuneki, T.Sasaoka
    • Organizer
      The 9th JSH Single Topic Conference "NASH 2010"(日本肝臓病学会主催)
    • Place of Presentation
      Grand Prince Hotel Takanawa
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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