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Novel function of oxytocin : its anorectic neuronal pathway and(patho) physiological role in regulating feeding

Research Project

Project/Area Number 22659044
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionJichi Medical University

Principal Investigator

YADA Toshihiko  自治医科大学, 医学部, 教授 (60166527)

Co-Investigator(Kenkyū-buntansha) NAKATA Masanori  自治医科大学, 医学部, 准教授 (10305120)
MAEJIMA Yuko  自治医科大学, 医学部, 助教 (40438669)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOxytocin / Nesfatin-1 / 摂食 / 体重 / 室傍核 / オキシトシン / POMC / 視床下部
Research Abstract

PVN Nesf neuron's downstream circuits and upstream regulators
(1) Histological and physiological data supported that the Oxt neuron in the hypothalamic PVN projects to the POMC neuron in the ARC, in addition to the NTS POMC neuron in the NTS as previously reported.
(2) Re-feeding following 48 hours fasting neither affected the mRNA levels for PVN Oxt and ARC POMC nor further increased the red fluorescence in the PVN of Oxt-mRFP-Tg rats.
(3) PVN Nesf neurons that regulate oxytocin neurons were activated directly by high glucose and insulin, the meal-evoked factors.
Peripheral administration of Oxt suppresses feeding and ameliorates obesity
(1) Oxt increased cytosolic Ca^<2+> in Nodose Ganglion Neurons isolated from the vagal afferent of mice.
(2) In high fat diet-induced obese mice, peripheral administration of Oxt ameliorated obesity, visceral fat accumulation, fatty liver and hyperglycemia, thereby showing ant-obesity and anti-metabolic syndrome effects.
Involvement of PVN Nesf-Oxt system in stress responses
(1) Restrain stress activated Nesf neurons in the stress-related nuclei.
(2) Central injection of Nesf activated noradrenalin, serotonin and CRH neurons and increased plasma levels of ACTH and glucocorticoid, which are key mediators of stress responses

Report

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

    (62 results)

All 2012 2011 2010 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (26 results) Book (12 results) Remarks (3 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass2011

    • Author(s)
      Maejima Y., Iwasaki Y., Yamahara Y., Kodaira M., Sedbazar U., Yada T.
    • Journal Title

      Aging(Albany NY)

      Volume: 3(12) Pages: 1169-1177

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22184277

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insulin suppresses ghrelin-induced calcium signaling in neuropeptide Y neurons of the hypothalamic arcuate nucleus2011

    • Author(s)
      Maejima Y., Kohno D., Iwasaki Y., Yada T.
    • Journal Title

      Aging(Albany NY)

      Volume: 3(11) Pages: 1092-1097

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22081645

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats2011

    • Author(s)
      Kohno D., Sone H., Tanaka S., Kurita H., Gantulga D., Yada T.
    • Journal Title

      Neuroscience Letters

      Volume: 499(3) Pages: 194-198

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21658429

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca^<2+> influx through L-type channels in mouse isletβ-cells2011

    • Author(s)
      Nakata M., Manaka K., Yamamoto S., Mori M., Yada T.
    • Journal Title

      Endocr. J.

      Volume: 58(4) Pages: 305-313

    • NAID

      10029588379

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21325742

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice2011

    • Author(s)
      Uchida K., Dezaki K., Damdindorj B., Inada H., Shiuchi T., Mori Y., Yada T., Minokoshi Y., Tominaga M.
    • Journal Title

      Diabetes

      Volume: 60(1) Pages: 119-126

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20921208

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca^<2+> influx through L-type channels in mouse islet β-cells2011

    • Author(s)
      Nakata M
    • Journal Title

      Endocr.J.

      Volume: 58 Pages: 305-313

    • NAID

      10029588379

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats2011

    • Author(s)
      Kohno D
    • Journal Title

      Neuroscience Letters

      Volume: 499 Pages: 194-198

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin suppresses ghrelin-induced calcium signaling in neuropeptide Y neurons of the hypothalamic arcuate nucleus2011

    • Author(s)
      Maejima Y
    • Journal Title

      Aging (Albany NY)

      Volume: 3 Pages: 1092-1097

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass2011

    • Author(s)
      Maejima Y
    • Journal Title

      Aging (Albany NY)

      Volume: 3 Pages: 1169-1177

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice.2011

    • Author(s)
      Uchida K
    • Journal Title

      Diabetes

      Volume: 60 Pages: 119-126

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca^<2+> influx through L-type channels in mouse islet β-cells.2011

    • Author(s)
      Nakata M
    • Journal Title

      Endocr.J.Epub ahead of print

    • NAID

      10029588379

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis2010

    • Author(s)
      Yoshida N., Maejima Y., Sedbazar U., Ando A., Kurita H., Damdindorj B., Takano E., Gantulga D., Iwasaki Y., Kurashina T., Onaka T., Dezaki K., Nakata M., Mori M., Yada T.
    • Journal Title

      Aging(Albany NY)

      Volume: 2(11) Pages: 775-784

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20966530

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotropin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus2010

    • Author(s)
      Toriya M., Maekawa F., Maejima Y., Onaka T., Fujiwara K., Nakagawa T., Nakata M., Yada T.
    • Journal Title

      Journal of Neuroendocrinology

      Volume: 22(9) Pages: 987-995

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20561155

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intra-islet PACAP protects pancreaticβ-cells against glucotoxicity and lipotoxicity2010

    • Author(s)
      Nakata M., Shintani N., Hashimoto H., Baba A., Yada T.
    • Journal Title

      J. Mol. Neurosci

      Volume: 42(3) Pages: 404-410

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20461496

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intra-islet PACAP protects pancreatic β-cells against glucotoxicity and lipotoxicity.2010

    • Author(s)
      Nakata M
    • Journal Title

      J.Mol.Neurosci.

      Volume: 42 Pages: 404-410

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotropin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus.2010

    • Author(s)
      Toriya M
    • Journal Title

      J.Neuroendocrinology

      Volume: 22 Pages: 987-995

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenalaxis.2010

    • Author(s)
      Yoshida N
    • Journal Title

      Aging (Albany NY)

      Volume: 2 Pages: 775-784

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 視床下部室傍核Nesfatin-1-Oxytocinによる摂食調節と病態的意義2011

    • Author(s)
      前島裕子
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] オキシトシンの摂食制御経路に弓状核POMCニューロンが関与する2011

    • Author(s)
      前島裕子
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] OLETFラットの過食・肥満は孤束核POMCと室傍核オキシトシンの低下による2011

    • Author(s)
      Sedbazar Udval
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 視床下部室傍核nesfatin-1ニューロンのレプチン、CCKによる活性化2011

    • Author(s)
      Gantulga Darambazar
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路
    • Related Report
      2011 Annual Research Report
  • [Presentation] グレリンによる膵ランゲルハンス島β細胞の新しいインスリン分泌制御2011

    • Author(s)
      出崎克也
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] 視床下部室傍核の新規摂食調節因子2011

    • Author(s)
      前島裕子
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] インスリンによるインスリン受容体カスケードを介した求心性迷走神経細胞Ca^<2+>シグナリング2011

    • Author(s)
      岩崎有作
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRPM2は細胞内Ca^<2+>濃度変化依存的及び非依存的にインスリン分泌を促進する2011

    • Author(s)
      内田邦敏
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nesfatin-1-regulated oxytocinergic signalling in the paraventricular nucleus causes anorexia via melanocortin pathway2010

    • Author(s)
      Maejima Y
    • Organizer
      46th EASD Annual Meeting
    • Place of Presentation
      Stockholm, Sweden
    • Related Report
      2011 Final Research Report
  • [Presentation] 中枢・交感神経の調節異常と食塩感受性2010

    • Author(s)
      矢田俊彦
    • Organizer
      第67回日本循環器心身医学会
    • Place of Presentation
      自治医科大学
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Nesfatin-1はオキシトシン-メラノコルチン系を介して摂食抑制する2010

    • Author(s)
      前島裕子
    • Organizer
      第31回日本肥満学会
    • Place of Presentation
      前橋
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes melanocortin-dependent anorexia2010

    • Author(s)
      Udval Sedbazar
    • Organizer
      日本味と匂学会第44回大会
    • Place of Presentation
      北九州
    • Related Report
      2011 Final Research Report
  • [Presentation] 視床下部室傍核Nesfatin-1はレプチン非依存性にOxytocin-POMC摂食抑制経路を作動する2010

    • Author(s)
      矢田俊彦
    • Organizer
      第28回内分泌代謝学サマーセミナー
    • Place of Presentation
      長崎
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 視床下部Nesfatin-1によるOxytocin・POMC依存性摂食抑制経路2010

    • Author(s)
      矢田俊彦
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Kv2.1-channel currents are mediated by phosphorylation of the channels during glucose stimulation.2010

    • Author(s)
      Yoshida M
    • Organizer
      The American Diabetes Association 70^<th> scientific sessions(Diabetes : 59(suppl.1)A454)
    • Place of Presentation
      Orlando, Florida
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nesfatin-1-regulated oxytocinergic signalling in the paraventricular nucleus causes anorexia via melanocortin pathway.2010

    • Author(s)
      Maejima Y
    • Organizer
      46^<th> EASD Annual Meeting
    • Place of Presentation
      Stockholm, Sweden
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRPM2とインスリン分泌2010

    • Author(s)
      内田邦敏
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Related Report
      2010 Annual Research Report
  • [Presentation] グレリンによるインスリン分泌制御2010

    • Author(s)
      出崎克也
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nesfatin-1は求心性迷走神経細胞の細胞内Ca^<2+>濃度を上昇させる:末梢Nesfatin-1の摂食抑制経路2010

    • Author(s)
      岩崎有作
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵β細胞Kv2.1チャネルの代謝依存性調節機構2010

    • Author(s)
      加計正文
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2010 Annual Research Report
  • [Presentation] グレリンによるβ細胞Kv2.1チャネル活性化を介したグルコース誘発インスリン分泌抑制2010

    • Author(s)
      出崎克也
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵島内インスリン分泌促進因子としてのNesfatin-12010

    • Author(s)
      中田正範
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2010 Annual Research Report
  • [Presentation] AAV1-mediated IL-10 gene-delivery improves glucose and energy metabolism in high-fat diet-induced obese mice.2010

    • Author(s)
      Nakata M
    • Organizer
      第16回日本遺伝子治療学会学術集会
    • Place of Presentation
      宇都宮
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes melanocortin-dependent anorexia.2010

    • Author(s)
      Udval Sedbazar
    • Organizer
      日本味と匂学会第44回大会
    • Place of Presentation
      北九州
    • Related Report
      2010 Annual Research Report
  • [Presentation] インスリンによる求心性迷走神経細胞活性化とシグナル伝達2010

    • Author(s)
      岩崎有作
    • Organizer
      第31回日本肥満学会
    • Place of Presentation
      前橋
    • Related Report
      2010 Annual Research Report
  • [Presentation] AgRPニューロンによる骨代謝2010

    • Author(s)
      笹沼秀幸
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Book] 中枢・末梢ネスファチンによる摂食制御と神経経路. Clinical Neuroscience2012

    • Author(s)
      前島裕子、Udval Sedbazar、矢田俊彦
    • Publisher
      中外医学社
    • Related Report
      2011 Final Research Report
  • [Book] Clinical Neuroscience2012

    • Author(s)
      前島裕子
    • Publisher
      中外医学社
    • Related Report
      2011 Annual Research Report
  • [Book] Nesfatin-1による摂食・糖代謝調節の機構と意義.実験医学2011

    • Author(s)
      前島裕子、矢田俊彦
    • Publisher
      羊土社
    • Related Report
      2011 Final Research Report
  • [Book] Nesfatin-1の摂食抑制神経経路およびストレス、循環、生殖における役割.日本薬理学雑誌2011

    • Author(s)
      前島裕子、Sedbazar Udval、岩崎有作、高野英介、矢田俊彦
    • Publisher
      金芳堂,日本薬理学会誌出版部
    • Related Report
      2011 Final Research Report
  • [Book] 膵臓の内分泌機能と炭水化物代謝の調節(翻訳). Inギャノング生理学.原書23版2011

    • Author(s)
      矢田俊彦
    • Publisher
      丸善出版株式会社
    • Related Report
      2011 Final Research Report
  • [Book] 日本薬理学雑誌2011

    • Author(s)
      前島裕子
    • Publisher
      金芳堂日本薬理学会誌出版部
    • Related Report
      2011 Annual Research Report
  • [Book] 実験医学2011

    • Author(s)
      前島裕子
    • Publisher
      羊土社
    • Related Report
      2011 Annual Research Report
  • [Book] 膵臓の内分泌機能と炭水化物代謝の調節(翻訳).Inギャノング生理学.原書23版2011

    • Author(s)
      矢田俊彦
    • Publisher
      丸善出版株式会社
    • Related Report
      2010 Annual Research Report
  • [Book] インスリン分泌におけるカルシウムシグナリングの役割. In糖尿病ナビゲーター第2版2010

    • Author(s)
      出崎克也、中田正範、矢田俊彦
    • Publisher
      メディカルビュー社
    • Related Report
      2011 Final Research Report
  • [Book] その他のインクレチン. In DPP-4阻害薬のすべて2010

    • Author(s)
      中田正範、矢田俊彦
    • Publisher
      先端医学社
    • Related Report
      2011 Final Research Report
  • [Book] その他のインクレチン.In DPP-4阻害薬のすべて2010

    • Author(s)
      中田正範
    • Publisher
      先端医学社
    • Related Report
      2010 Annual Research Report
  • [Book] インスリン分泌におけるカルシウムシグナリングの役割.In糖尿病ナビゲーター第2版2010

    • Author(s)
      出崎克也
    • Publisher
      メディカルビュー社
    • Related Report
      2010 Annual Research Report
  • [Remarks] 新聞掲載日本経済新聞夕刊平成23年12月21日(水曜日)読売新聞朝刊平成23年12月25日(日曜日)新聞掲載

    • Related Report
      2011 Final Research Report
  • [Remarks] ホームページ掲載URL :日本経済新聞(電子版)平成23年12月21日(水曜日) 10 : 34

    • URL

      http://www.nikkei.com/news/category/article/g=96958A9C93819695E0E2E2E6E78DE0E3E3E0E0E2E3E39180E2E2E2E2;at=ALL

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/physio2/physiol_new_HP2008/index.htm

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 肥満・メタボリックシンドローム治療薬、及びその動物の治療方法2011

    • Inventor(s)
      矢田俊彦(届出・代表)、前島裕子、岩崎有作
    • Industrial Property Rights Holder
      自治医科大学
    • Industrial Property Number
      2011-271652
    • Filing Date
      2011-12-12
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 食欲調整剤、治療薬、健康食品、動物用飼料、及び食欲調整方法2011

    • Inventor(s)
      矢田俊彦(届出・代表)、栗田英治、シューカイ
    • Industrial Property Rights Holder
      自治医科大学
    • Industrial Property Number
      2011-177985
    • Filing Date
      2011-08-16
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 食欲調整剤、治療薬、健康食品、動物用飼料、及び食欲調整方法2011

    • Inventor(s)
      矢田俊彦
    • Industrial Property Rights Holder
      自治医科大学
    • Industrial Property Number
      2011-177985
    • Filing Date
      2011-08-16
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 肥満・メタボリックシンドローム治療薬、及びその動物の治療方法2011

    • Inventor(s)
      矢田俊彦
    • Industrial Property Rights Holder
      自治医科大学
    • Industrial Property Number
      2011-271652
    • Filing Date
      2011-12-12
    • Related Report
      2011 Annual Research Report

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

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