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2011 Fiscal Year Final Research Report

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

Research Project

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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
KeywordsOxytocin / Nesfatin-1 / 摂食 / 体重 / 室傍核
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

  • Research Products

    (27 results)

All 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (9 results) Book (6 results) Remarks (2 results) Patent(Industrial Property Rights) (2 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

    • 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

    • 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

    • 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

    • URL

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

    • 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

    • 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

    • 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

    • 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

    • 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
    • Year and Date
      20110923-24
  • [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
    • Year and Date
      20110923-24
  • [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
    • Year and Date
      20110923-24
  • [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
    • Year and Date
      20101127-28
  • [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
    • Year and Date
      20101001-02
  • [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
    • Year and Date
      20100920-24
  • [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
    • Year and Date
      20100908-10
  • [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
    • Year and Date
      20100708-10
  • [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
    • Year and Date
      20100519-20
  • [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
    • Total Pages
      181-183
    • Publisher
      中外医学社
  • [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
    • Total Pages
      1240-1241
    • Publisher
      羊土社
  • [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
    • Total Pages
      162-165
    • Publisher
      金芳堂,日本薬理学会誌出版部
  • [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
    • Total Pages
      370-396
    • Publisher
      丸善出版株式会社
  • [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
    • Total Pages
      50-51
    • Publisher
      メディカルビュー社
  • [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
    • Total Pages
      47-51
    • Publisher
      先端医学社
  • [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

  • [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

  • [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
      特許、特願2011-271652
    • Filing Date
      2011-12-12
  • [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
      特許、特願2011-177985
    • Filing Date
      2011-08-16

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Published: 2013-07-31  

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