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Impact of the cooperative effect of estrogen and orexin on abnormalities with emotion and metabolism in menopausal mice

Research Project

Project/Area Number 15K15599
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionUniversity of Toyama

Principal Investigator

Sasaoka Toshiyasu  富山大学, 大学院医学薬学研究部(薬学), 教授 (00272906)

Co-Investigator(Kenkyū-buntansha) 和田 努  富山大学, 大学院医学薬学研究部(薬学), 講師 (00419334)
恒枝 宏史  富山大学, 大学院医学薬学研究部(薬学), 准教授 (20332661)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsオレキシン / エストロゲン / 閉経期 / 糖代謝 / インスリン抵抗性 / 日内リズム / ストレス / うつ / 耐糖能異常 / 慢性炎症 / 脂質代謝 / 閉経
Outline of Final Research Achievements

We examined the cooperative protective role of estrogen and orexin in abnormalities with emotion and metabolism in menopausal mice. Female, but not male mice, were protected against metabolic abnormalities fed high-fat diet. The additional orexin deficiency induced the metabolic abnormalities in the female mice. Ovariectomized orexin knockout mice fed high-fat diet presented excessive weight gain and impaired glucose tolerance. The impaired glucose tolerance was ameliorated when estrogen was administered intracerebroventricularly to the ovariectomized high-fat fed mice. However, the beneficial effect of estrogen was disappeared in the ovariectomized mice lacking orexin. These results indicate that estrogen and orexin cooperatively regulate glucose and energy homeostasis in female mice.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (24 results)

All 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice.2016

    • Author(s)
      Tsuneki H, Kon K, Ito H, Yamazaki M, Takahara S, Toyooka N, Ishii Y, Sasahara M, Wada T, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology.

      Volume: 157 Issue: 11 Pages: 4146-4157

    • DOI

      10.1210/en.2016-1404

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sleep Control, GPCRs, and Glucose Metabolism.2016

    • Author(s)
      Tsuneki H, Sasaoka T, Sakurai T.
    • Journal Title

      Trends Endocrinol Metab.

      Volume: 27(9) Issue: 9 Pages: 633-42

    • DOI

      10.1016/j.tem.2016.06.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nighttime administration of nicotine improves hepatic glucose metabolism via the hypothalamic orexin system in mice.2016

    • Author(s)
      Tsuneki H, Nagata T, Fujita M, Kon K, Wu N, Takatsuki M, Yamaguchi K, Wada T, Nishijo H, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology

      Volume: 157 Issue: 1 Pages: 195-206

    • DOI

      10.1210/en.2015-1488

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Orexin regulates glucose homeodynamics with daily rhythm.2015

    • Author(s)
      Tsuneki H, Wada T, Sasaoka T.
    • Journal Title

      Orexin and Sleep. Springer International Publishing Switzerland

      Volume: 2015 Pages: 381-394

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Dual orexin receptor antagonist ameliorates impaired sleep/wake cycle and glucose metabolism in diabetic db/db mice in a treatment-time dependent manner.2016

    • Author(s)
      Kon K, Tsuneki H, Wada T, Sasaoka T.
    • Organizer
      The 15th Japan-Korea Diabetic Nephropathy Seminar
    • Place of Presentation
      Asahikawa
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] オレキシンによる睡眠・覚醒と糖代謝調節.2016

    • Author(s)
      笹岡利安.
    • Organizer
      第43回日本神経内分泌学会学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] The ameliorating effect of suvorexant, a dual orexin receptor antagonist, on glucose metabolism in type 2 diabetic db/db mice.2016

    • Author(s)
      Tsuneki H, Kon K, Wada T, Sasaoka T.
    • Organizer
      52nd EASD Annual Meeting
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 概日リズムに基づいたオレキシン系の活性化による糖代謝異常治療戦略.2016

    • Author(s)
      笹岡利安,恒枝宏史.
    • Organizer
      日本睡眠学会第41回定期学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 糖尿病と睡眠.2016

    • Author(s)
      笹岡利安.
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 不眠症治療薬スボレキサントによる視床下部オレキシン系を介した糖代謝改善効果.2016

    • Author(s)
      今 寛太,恒枝宏史,和田 努,笹岡利安.
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 中枢性糖代謝調節機構におけるドパミンD2受容体系の機能的意義の解析.2016

    • Author(s)
      恒枝宏史,東海絵美,髙月真由美,大西兼悟,今 寛太,和田 努,笹岡利安.
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 視床下部オレキシンによる睡眠と糖代謝の連係調節の意義.2016

    • Author(s)
      恒枝宏史,和田 努,笹岡利安.
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 視床下部オレキシンの「動的」血糖制御を標的とした糖尿病治療の新戦略.2016

    • Author(s)
      恒枝宏史,和田 努,笹岡利安.
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] オレキシン受容体拮抗薬による2型糖尿病マウスの睡眠と肝糖代謝の改善効果.2016

    • Author(s)
      恒枝宏史,今 寛太,和田 努,笹岡 利安.
    • Organizer
      第3回肝臓と糖尿病・代謝研究会
    • Place of Presentation
      金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] 雌性オレキシン欠損マウスが高度肥満および脂肪組織の慢性炎症を呈する機序の解析.2016

    • Author(s)
      越田千晶,恒枝宏史,浅岡健広,和田 努,笹岡利安.
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] 視床下部オレキシンによる自律神経系と小胞体ストレス応答を介したマウス肝糖産生の調節機構.2015

    • Author(s)
      笹岡利安,和田 努,恒枝宏史.
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] オレキシン系を標的とした生体リズム制御による2型糖尿病マウスの糖代謝改善効果.2015

    • Author(s)
      今 寛太,恒枝宏史,東海絵美,永田貴嗣,和田 努,笹岡利安.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 制御性T細胞の性特異的な脂肪組織局在が肥満に伴う慢性炎症と糖代謝に及ぼす影響.2015

    • Author(s)
      伊藤哲生,和田 努,樫村彩香,王生美沙,恒枝宏史,鮫島 梓,齋藤 滋,笹岡利安.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Hypothalamic orexin as a chronotherapeutic target for type 2 diabetes.2015

    • Author(s)
      Tsuneki H, Nagata T, Kon K, Wada T, Sasaoka T.
    • Organizer
      American Diabetes Association (ADA) 75th Scientific Sessions
    • Place of Presentation
      Boston, U.S.A.
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 視床下部オレキシンによる加齢および肥満病態での脂肪組織機能の防御効果の解析.2015

    • Author(s)
      東海絵美,恒枝宏史,浅岡健広,今 寛太,髙橋佳佑,越田千晶,布目幸久,和田 努,笹岡利安.
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規不眠症治療薬スボレキサントの時間治療による2型糖尿病マウスの糖代謝改善効果.2015

    • Author(s)
      今 寛,恒枝宏史,和田 努,笹岡利安.
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] ニコチン作用から見た視床下部オレキシン系の日内リズム調節が高血糖に及ぼすインパクト.2015

    • Author(s)
      恒枝宏史,永田貴嗣,藤田樹生,和田 努,笹岡利安.
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] 自律神経系の概日リズムとオレキシン. Annual Review 2016 糖尿病・代謝・内分泌.2016

    • Author(s)
      笹岡利安, 恒枝宏史.
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2016 Annual Research Report
  • [Remarks] 富山大学 大学院医学薬学研究部(薬学系) 病態制御薬理学研究室

    • URL

      http://www.pha.u-toyama.ac.jp/clinphar/index-j.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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