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Control of metabolic diseases by means of brain function in mammals

Research Project

Project/Area Number 08306016
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI Michio  The University of Tokyo, Graduate School of Agricultural and Life Science, Professor, 大学院・農学生命科学研究科, 教授 (30011943)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Noboru  Miyazaki University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (80150192)
TSUJIMOTO Hajime  The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (60163804)
KAI Chieko  The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (10167330)
MORI Yuji  The University of Tokyo, Graduate School of Agricultural and Life Science, Profe, 大学院・農学生命科学研究科, 教授 (40157871)
NISHIHARA Masugi  The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (90145673)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥21,800,000 (Direct Cost: ¥21,800,000)
Fiscal Year 1998: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1997: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1996: ¥10,800,000 (Direct Cost: ¥10,800,000)
KeywordsHypothalamus / Feeding behavior / Metabolism / Diabetes mellitus / Obesity / Growth hormone / Leptin / Transgenic rats
Research Abstract

The purpose of this study was to elucidate hypothalamic neuronal mechanisms controlling metabolism and feeding behavior and to regulate obesity, diabetes and abnormal feeding. We produced transgenic rats expressing human growth hormone (hGH), hGH receptor (hGHR) and leptin. The hGH transgenic rats showed excessive obesity due to the lack of endogenous GH pulses. On the other hand, in the bigenic rats expressing both hGH and hGHR, adipose tissue mass and serum leptin levels were decreased. These animals are useful models to analyze GH pulsatility and lipid metabolism. In the present study, we also examined the effect of injection of anti sense oligodeoxynucleotides (ODNs) of GABA synthetic enzyme, glutamic acid decarboxylase (GAD) that consists of two isozymes, GAD65 and GAD67, into the VMH of the male rat on food intake, body weight and locomotor activity. The results suggested that GAD65 was mainly involved in enhancing food intake and suppressing locomotor activity in rat VMH.This study also indicates that central injection of antisense oligodeoxynucleotides is useful means to regulate animal metabolism. From these studies, symptoms such as obesity, diabetes and abnormal feeding may be controlled by regulating GH pulsatility and gene expression of GAD 65 in they hypothalamus.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Chang KT,他: "Production of transgenic rats and mice by the testis-mediated gene transfer" Journal of Reproduction and Development. 45. 29-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chang KT,他: "Possible mechanisms for the testis-mediated gene transfer as a new method for producing transgenic animals" Journal of Reproduction and Development. 45. 37-42 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bannai M,他: "Water-absorbent polymer as a carrier for a discrete deposit of antisense oligodeoxynucleotides in the central nervous system" Brain Research Protocols. 3. 83-87 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda A,他: "Obesity and insulin resistance in human growth hormone(hGH)transgenic rats" Endocrinology. 139. 3057-3063 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirasawa M,他: "Activity of the ventromedial hypothalamic neurons suppressing heart rate is associated with paradoxical sleep in the rat" Brain Research. 797. 103-108 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bannai M,他: "Effect of injection of antisense oligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. 784. 305-315 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Narita K,他: "Neuronal Mechanisms for Generating Locomotor Activity" Kiehn O,Harris-Warrick RM,Jordan LM,Hultborn H,Kudo N(eds),The New York Academy of Sciences, 573 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki M,他: "Reproductive Biology Update : Novel Tools for Assessment of Environmental Toxicity" Miyamoto H,Manabe N(eds),Nakanishi Printing Co., 498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chang KT,et al.: "Production of transgenic rats and mice by the testit-mediated gene transfer" Journal of Reproduction and Development. 45. 29-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chang KT,et al.: "Possible mechanisms for the testis-mediated gene transfer as a new method for producing transgenic animals" Journal of Reproduction and Development. 45. 37-42 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bannai M,Et el.: "Water-absorbent polymer as a carrier for a discrete deposit of antisense oligodeoxynucleotides in the central nervous system" Brain Research Protocols. 3. 83-87 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda A,et al.: "Obesity and insulin resistance in human growth hormone (hGH) transgenic rats" Endocrinology. 139. 3057-3063 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirasawa M,et al.: "Activity of the ventromedial hypothalamic neurons suppressing heart rate is associated with paradoxical sleep in the rat" Brain Research. 797. 103-108 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bannai M,et al.: "Effect of injection of antisense oligonucleotides GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. 784. 305-315 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Narita K,et al.: Neuronal Mechanisms for Generating Locomotor Activity (Kichn O,Harris-Warrick RM,Jordan LM,Hultborn H,Kudo N (eds). The New York Academy of Sciences, 573 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki M, et al.: Reproductive Biology Update : Novel Tools for Assessment of Environmental Toxicity (Miyamoto H,Manabe N (eds). Nakanishi Printing Co., 498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chang KT,他: "Production of transgenic rats and mice by the testis-mediated gene transfer" Journal of Reproduction and Development. 45. 29-36 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Chang KT,他: "Possible mechanisms for the testis-mediated gene transfer as a new method producing transgenic animals" Journal of Reproduction and Development. 45. 37-42 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Bannai M,他: "Water-absorbent polymer as a carrier for a discrete deposit of antisense oligodeoxynucleotides in the central nervous system" Brain Research Protocols. 3. 83-87 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda A,他: "Obesity and insulin resistance in human growth hormone(hGH)transgenic rats" Endocrinilogy. 139. 3057-3063 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirasawa M,他: "Activity of the ventromedial hypothalamic neurons suppressing heart rate is associated with paradoxical sleep in the rat" Brain Research. 797. 103-108 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Bannai M,他: "Effect of injection of antisense oligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. 784. 305-315 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Narita K,他: "Neuronal Mechanisms for Generating Locomotor Activity" Kiehn O,Harris-Warrick RM,Jordan LM,Hultborn H,Kudo N(eds),The New York Academy of Sciences, 573 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki M,他: "Reproductive Biology Update:Novel Tools for Assessment of Environmental Toxicity" Miyamoto H,Manabe N(eds),Nakanishi Printing Co., 498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Bannai M: "Effect of injection of antisense oligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida S: "A novel steroid inhibitor for a rat 20α-hydroxysteroid dehydrogenase isozyme (HSD1)" Biology of Reproduction. 57. 1433-1437 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamanouchi K: "Inhibin α-subunit mRNA is expressed in the corpus luteum of the pregnant mare" Journal of Reproduction and Development. 43. 267-270 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda A: "Different female reproductive phenotypes determined by human growth hormone (hGH) levels in hGH-transgenic rats" Biology of Reproduction. 56. 847-851 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoo MJ: "Involvement of prostaglandins in suppression of gonadotropin-releasing hormone pulse generator activity by tumor necrosis factor-α" Journal of Reproduction and Development. 43. 181-187 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoo MJ: "Tumor necrosis factor-α mediates mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generatator activity in the rat" Endocrine Journal. 44. 141-148 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki M: "Reproductive Biology Update : Novel Tools for Assesment of Enviromental Toxicity" Miyamoto H,Manabe N (eds),Nakanishi Printing Co., 498 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishihara M: "Neural Control of the Reproduction : Physiology and Behavior" Maeda K,Tsukamura H,Yokoyama A (eds),Karger, 254 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mi-Jeong Yoo: "Tumor necrosis factor-α mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat." Endocrine Journal. 44. 141-148 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirotaka Kanuka: "Prolactin expresses differential effect on apoptotic cell death of luteal cells in vivo and in vitro." Endocrine Journal. 44. 11-22 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shuichi Onami: "Splenic macrophages alter the steroidgenesis of Leydig cells in vitro." Endocrine Journal. 43. 477-485 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michiru Hirasawa: "The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus." Brain Research. 724. 186-190 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fusae Nishimura: "Changes in chemical sensitivity of rat ventromedial hypothalamic neurons by food deprivation." Physiology & Behaviour. 60. 7-12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michiru Hirasawa: "Neural activity in the VMH associated with suppression of the circulatory system in rats." Physiology & Behaviour. 59. 1017-1023 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masugi Nishihara: "Neural Control of the Reproduction:Physiology and Behavior." Yokoyama A(ed),Japan Scientific Societies Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 高橋迪雄: "ヒューマン・サイエンス:生殖機能と下垂体前葉機能調節係" コロナ社(印刷中), (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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