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Mechanism of failure of appetite regulating system in obesity

Planned Research

Project AreaMolecular Basis and Disorders of Control of Apetite and Fat Accumulation
Project/Area Number 22126010
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInternational University of Health and Welfare (2013-2014)
Takasaki University of Health and Welfare (2012)
Kiryu University (2010-2011)

Principal Investigator

SHIMIZU Hiroyuki  国際医療福祉大学, 大学病院, 教授 (20251100)

Co-Investigator(Kenkyū-buntansha) OSAKI Aya  群馬大学, 医学部附属病院, 医員 (30711387)
Co-Investigator(Renkei-kenkyūsha) TSUCHIYA Takafumi  獨協医科大学, 越谷分院, 講師 (20396659)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥88,400,000 (Direct Cost: ¥68,000,000、Indirect Cost: ¥20,400,000)
Fiscal Year 2014: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2013: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2012: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2011: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2010: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Keywordsネスファチン / 血圧 / 腎臓 / 脂肪肝 / ミトコンドリア / 骨格筋 / 体重変動 / 肥満 / 過食 / ネスファチン-1 / 食行動調節 / 高脂肪食 / 視床下部 / 脂肪組織
Outline of Final Research Achievements

The present study used Nesf (nesfatin) transgenic (Tg) mice to investigate the metabolic role of Nesf. No differences were observed in daily food intake and body weight. Nesf Tg mice showed decreased mRNA expression of CART. Nesf Tg mice fed 45% high-fat diet (HFD) showed higher increase in body weight than their non-Tg littermates; however, no difference was observed in daily food intake between these 2 groups. Nesf Tg mice fed 45% HFD showed a significant increase in the weight of the liver, subcutaneous fat, and brown adipose tissue and decrease in the expression of uncoupling protein-1 in the subcutaneous fat. Insulin levels of these Tg mice were significantly higher. Histological analysis showed marked fat deposition in the hepatocytes surrounding the hepatic central veins in Nesf/NUCB2 Tg mice fed 45% HFD. It is indicated that Nesf/NUCB2 is involved in the development of insulin resistance and fat deposition in the liver, independent of the modulation of energy intake.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2015 2014 2013 2012 2011 2010

All Journal Article (13 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (14 results)

  • [Journal Article] Possible involvement of anorexigenic protein, nesfatin/nucleobindin-2 (NUCB2) in blood pressure regulation by regulating water reabsorption in renal collecting duct.2014

    • Author(s)
      Shimizu H and Osaki A
    • Journal Title

      J Cytology and Histology

      Volume: 5 Pages: 290-290

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.2014

    • Author(s)
      Suzuki Y, Shimizu H, Ishizuka N, Kubota N, Kubota T, Senoo A, Kageyama H, Osaka T, Hirako S, Kim HJ, Matsumoto A, Shioda S, Mori M, Kadowaki T, Inoue S.
    • Journal Title

      Diabetes.

      Volume: 63(5) Issue: 5 Pages: 1637-1648

    • DOI

      10.2337/db13-0636

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral administration of nesfatin-1 increases blood pressure in mice.2013

    • Author(s)
      Osaki A, Shimizu H
    • Journal Title

      Hypertension Research

      Volume: 37 Issue: 2 Pages: 185-186

    • DOI

      10.1038/hr.2013.122

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation.2013

    • Author(s)
      Katano-Toki A, Satoh T, Tomaru T, Yoshino S, Ishizuka T, Ishii S, Ozawa A, Shibusawa N, Tsuchiya T, Saito T, Shimizu H, Hashimoto K, Okada S, Yamada M, Mori M
    • Journal Title

      Molecular Endocrinology

      Volume: 27 Issue: 5 Pages: 769-780

    • DOI

      10.1210/me.2012-1332

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nesfatin-1: its role in the diagnosis and treatment of obesity and some psychiatric disorders.2013

    • Author(s)
      Shimizu H, Mori M
    • Journal Title

      Methods Mol Biol

      Volume: 963 Pages: 327-338

    • DOI

      10.1007/978-1-62703-230-8_20

    • ISBN
      9781627032292, 9781627032308
    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
  • [Journal Article] Discovery of nesfatin-1 and overview of biological actions and new developments.2013

    • Author(s)
      Mori M, Yamada M, Okada S, Hashimoto K, Satoh T, Shimizu H, Yada T
    • Journal Title

      Curr Pharm Des

      Volume: 19 Pages: 6921-6928

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Enhanced expression of nucleobindin-2 in white adipose tissue of ventromedial-lesioned rats.2012

    • Author(s)
      Aya Osaki
    • Journal Title

      Neuroscience Letters

      Volume: 521 Issue: 1 Pages: 46-51

    • DOI

      10.1016/j.neulet.2012.05.056

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nesfatin-1 Induces the Phosphorylation Levels of cAMP Response Element-Binding Protein for Intracellular Signaling in a Neural Cell Line.2012

    • Author(s)
      Ishida E
    • Journal Title

      PLoS One

      Volume: 7(12) Issue: 12 Pages: e50918-e50918

    • DOI

      10.1371/journal.pone.0050918

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell proliferation in visceral organs induced by ventromedial hypothalamic (VMH) lesions : Development of electrical VMH lesions in mice and resuiting pathophysiological profiles2011

    • Author(s)
      Suzuki Y, Shimizu H, et al
    • Journal Title

      Endocrine Journal

      Volume: 58巻 Pages: 247-256

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon plays an important role in the modification of insulin secretion by leptin2011

    • Author(s)
      Shimizu H, et al
    • Journal Title

      Islets

      Volume: 3巻 Pages: 150-154

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males.2010

    • Author(s)
      Tsuchiya T, Shimizu H, et al.
    • Journal Title

      Clinical Endocrinology

      Volume: 第73巻 Pages: 484-490

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Troglutazone, a ligand of PPARγ, stabilizes NUCB2 (nesfatin) mRNA by activating the ERK1/2 pathway : isolation and characterization of the human NUCB2 gene.2010

    • Author(s)
      Yamada M,, Shimizu H, et al.
    • Journal Title

      Endocrinology

      Volume: 第151巻 Pages: 2494-2503

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early-stage atherosclerosis.2010

    • Author(s)
      Ando T,, Shimizu H, et al.
    • Journal Title

      Diabetic Medicine

      Volume: 第27巻 Pages: 1430-1435

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ネスファチン/ヌクレオビンディン-2 (nesf/NUCB2) 過剰発現マウスの代謝解析2015

    • Author(s)
      清水弘行、田中満崇
    • Organizer
      第74回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関、山口県
    • Year and Date
      2015-05-21 – 2015-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] ネスファチン/ヌクレオビンディン-2 (Nesf/NUCB2) 過剰発現マウスの代謝解析2015

    • Author(s)
      清水弘行、田中満崇、大崎 綾
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市、山口県
    • Year and Date
      2015-05-21 – 2015-05-24
    • Related Report
      2013 Annual Research Report
  • [Presentation] Transgenic mice overexpressing nesfatin/nucleobindin-2 (Nesf/NUCB2) are susceptible to high fat diet (HFD)-induced obesity.2015

    • Author(s)
      Shimizu H
    • Organizer
      ENDO 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-03-05 – 2015-03-08
    • Related Report
      2013 Annual Research Report
  • [Presentation] ネスファチン/ヌクレオビンディン-2 過剰発現は、高脂肪食摂餌時の体重増加を促進する2014

    • Author(s)
      清水弘行、荒井桃子、田邊裕子、大崎 綾
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎市、宮崎県
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2013 Annual Research Report
  • [Presentation] Possible involvement of anorexigenic protein, nesfatin/nucleobindin-2 (NUCB2) in blood pressure regulation by regulating water reabsorption in renal collecting duct.2014

    • Author(s)
      Shimizu H, Osaki A
    • Organizer
      74th Scientific Sessions of American Diabetes Association
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 摂食抑制蛋白、ネスファチン/ヌクレオビンディン-2 (Nesf/NUCB2) の循環調節機構への関与2013

    • Author(s)
      清水弘行、大崎 綾、小保方優、小板橋紀通、江口広志、森 昌朋
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京、東京都
    • Year and Date
      2013-10-12
    • Related Report
      2013 Annual Research Report
  • [Presentation] Paradoxical reduction of body weight gain in mice lacking an anorexigenic protein, nesfatin/nucleobindin-22013

    • Author(s)
      Shimizu H, Osaki A, Ehuchi H, Senoo A
    • Organizer
      73rd Annual Meeting of American Diabetes Association
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2013-06-21 – 2013-06-25
    • Related Report
      2013 Annual Research Report
  • [Presentation] Paradoxical Reduction of Body Weight Gain in Mice Lacking an Anorexigenic Protein, Nesfatin/Nucleobindin-22013

    • Author(s)
      Hiroyuki Shimizu
    • Organizer
      73rd scientific sessions of American Diabetes Association
    • Place of Presentation
      シカゴ市
    • Year and Date
      2013-06-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] ネスファチン/ヌクレオビンディン-2 (Nesf/NUCB2) 欠損の糖代謝への影響2013

    • Author(s)
      大崎 綾、清水弘行、瀬野尾章、江口広志
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市、熊本県
    • Year and Date
      2013-05-18
    • Related Report
      2013 Annual Research Report
  • [Presentation] ネスファチン/ヌクレオビンディン-2 (Nesf/NUCB2) 欠損マウスの糖代謝への影響2013

    • Author(s)
      清水弘行
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市
    • Year and Date
      2013-05-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] ネスファチン/ヌクレオビンディン-2 (nesf/NUCB2) 欠損による体重抑制2013

    • Author(s)
      大崎 綾
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台市
    • Year and Date
      2013-04-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 末梢臓器に発現するネスファチン/ヌクレオビンディン-2 (NUCB2) 免疫活性の局在に関する検討.。2012

    • Author(s)
      清水弘行
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都市
    • Year and Date
      2012-10-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Enhanced expression of nesfatin/nucleobindin-2 (NUCB2) in white adipose tissue of ventromedial hypothalamus (VMH)-lesioned rats.2012

    • Author(s)
      Aya Osaki
    • Organizer
      72nd scientific sessions of American Diabetes Association
    • Place of Presentation
      米国フィラデルフィア市
    • Year and Date
      2012-06-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 視床下部腹内側核破壊ラットにおけるネスファチン/ヌクレオビンディン-2(Nesf/NUCB2)発現変動に関する検討。2012

    • Author(s)
      大崎 綾
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2018-03-28  

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