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Treatment of obesity and diabetes by the neuronal factor

Research Project

Project/Area Number 10470233
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionOITA MEDICAL UNIVERSITY

Principal Investigator

SAKATA Toshiie  Oita medical university, school of medicine, Professor, 医学部, 教授 (50037420)

Co-Investigator(Kenkyū-buntansha) YOSHIMATSU Hironobu  Oita medical university, school of medicine, Associate Professor, 医学部, 助教授 (00166993)
浜口 和之  大分医科大学, 医学部, 講師 (60180931)
黒川 衛  大分医科大学, 医学部, 助手 (70301380)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsEnergy homeostasis / Uncoupling protein / Neuronal histamine / Leptin / Diabetes / ヒスタミン受容体1ノックアウトマウス / db / dbマウス / UCP / エネルギー代謝調節 / 肥満糖尿病 / 内臓脂肪 / agouti related ptotain / 高インスリン血症 / Zucker fatty rat / Yellow Ay mice / MC4-R / uncoupling protain / agouti related protein / uncoupling protein
Research Abstract

We analyze energy homOastasis including uncoupling protein (UCF) family mRNA expression in diabetic state. UCP1 mRNA expression in brown adipose tissue (BAT) was decreased in storeptozocin (STZ)-induced diabetes rat compared with control rats. UCP2 mRNA in BAT, white adipose tissue (WAT), and skeletal muscle (MSL) were increased in STZ diabetic rat. In contrast, UCP3 mRNA, not UCP2 mRNA, was increased in heart concomitantly increase with free fatty acid (EFA). However, heart UCP3 mRNA was not increased in zucker fatty obese rats which shown chromic hyper free fatty acidemia. These results indicated that UCP family mRNA expressions were tissue-dependently regulated in diabetic state and heart UCP3 mRNA was regulated FFA in acute phase. We next analyze energy homeostasis regulated by neuronal histamine. Visceral adiposity and ob mRNA expression in WAT were increased in histamine H_1, receptor (H_1R) knockout (H1KO) mice. In addition, the effects of leptin on food intake and BAT UCP1 mRNA expression were attenuated in H1KO mice. Furthermore, central administration of histamine decreased daily food intake and BAT UCP1 mRNA expression even in leptin resistant db/db obese mice. These studies demonstrated that neuronal histamine including H_1 -R is the target of leptin in food intake, adiposity, BAT UCP1 mRNA expression and neuronal histamine can act energy homeostasis during leptin resistant obesity.

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Sakata T, et al.: "Hypothalamic neuronal histamine: Implications of its homeostatic control of energy metabolism"Nutrition. 13. 403-411 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimatsu H, et al.: "Hypothalamic neuronal histamine as a target of leptin in feeding behavior"Diabetes. 48. 2286-2291 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hidaka S, et al.: "Streptozotocin treatment upregulates uncoupling protein 3 expression in the rat heart"Diabetes. 48. 430-435 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masaki T, et al.: "Targeted Disruption ofHistamine Hi-Receptor Attenuates Regulatory Effects ofLeptin on Feeding, Adiposity and UCP Family in Mice"Diabetes. 50. 385-391 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakata T, Yoshimatsu H, Kurokawa M.: "Hypothalamic neuronal histamine : Implications of its homeostatic control of energy metabolism"Nutrition. 13. 403-411 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimatsu H, Itateyama E, Kondou S, Tajima D, k. Himeno, Hidaka S, Kurokawa M, Sakata T.: "Hypothalamic neuronal histamine as a target of leptin in feeding behavior"Diabetes. 48. 2286-2291 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hidaka S, Kakuma T, Yoshimatsu H, Sakino H, Fukuchi S, Sakata T.: "Streptozotocin treatment upregulates uncoupling protein 3 expression in the rat heart"Diabetes. 48. 430-435 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masaki T, Yoshimatsu H, Chiba S, Watanabe T, Sakata T.: "Targeted Disruption of Histamine H1 -Receptor Attenuates Regulatory Effects of Leptin on Feeding, Adiposity and UCP Family in Mice"Diabetes. 50. 385-391 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masaki T, et al: "Central Infusion of Histamine Reduces Fat Accumulation and Up-regulates USP Family in Leptin Resistant Obese Mice"Diabetes. 50,. 376-384 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaki T, et al: "Targeted Disruption of Histamine H1-Receptor Attenuates Regulatory Effects of Leptin on Feeding, Adiposity and UCP Family in Mice"Diabetes. 50,. 385-391 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kondou S, et al: "Molecular cloning of rat brain mitochondrial carrier protein-1 cDNA and its up-regulation during postnatal development"BBA. 1457. 182-189 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaki T, et al: "mpaired response of UCP family to cold exposure in diabetic (db/db) mice"AJP. 279(4). 1305-1309 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tastukawa M, et al: "Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese"PSEBM. 223(2). 156-162 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hanada R, et al: "Differential regulation of melanin-concentrating hormone and orexin genes in the agouti-related protein/melanocortin-4 receptor system"BBRC. 5;268(1). 88-91 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakata T, et al.: "Control Mechanisms of Stress and Emotion : Neuroendocrine-Based Studies."Eds.by Yamashita H,Funder JW,Verbails JG,Ueta Y,Endo Y,Elsevier. 359 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakata T, et al.: "Progress in Obesity Research 1998"Eds.by B.Guy-Grand and G.Aihoud,John Libbey. 679 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshimatsu H,et al.: "Hypothalamic neuronal histamine as a target of leptin in feeding behavior"Diabetes. 48. 2286-2291 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masaki T,et al.: "Up-regulation of uterine UCP2 and UCP3 in pregnant rats"BBA. 1440. 81-85 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hidaka S,et al.: "Streptozotocin treatment upregulat Yoshimatsu H,et ales uncoupling protein 3 expression in the rat heart"Diabetes. 48. 430-435 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kang M,et al.: "Prostaglandin E2 mediates activation of hypothalamic histamine by interleukin-1 βin rats"Proc Exp Biol Med. 220. 88-93 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masaki T,et al.: "Induction of rat uncoupling protein-2 gene treated with tumour necrosis factor alpha in vivo"Eur j Clin Invest. 29. 76-82 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masaki T,et al.: "Tumor necrosis factor-α regulates in vivo expression of the rat UCP family differentially"BBA. 1436. 585-592 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakata T,et al.: "Control Mechanisms of Stress and Emotion:Neuroendocrine-Based Studies."Eds.by Yamashita H,Funder JW,Verbails JG,Ueta Y,Endo Y,Elsevier. 359 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakata T,et al.: "Progress in Obesity Research 1998"Eds.by B.Guy-Grand and G.Aihoud,Jhon Libbey. 679 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shuji Hidaka,et al.: "Streptozotocin treatment upregulates uncoupling prothein 3 expression in the rat heart." Diabetes. 48. 430-435 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takayuki Masaki,et al.: "Tumor necrosis factor-α regulates in vivo expression of the rat UCP family differentially." Bioch Biophy Acta. 1436. 585-592 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasushi Teshima,et al.: "Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothvronine during postnatal period in rats." Bioch Biophy Acta. 1448. 409-415 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masahiro Kang,et al.: "Prostaglandin E2 mediates activation of hypothalamic histamine by interleukinl β in rats." Proc Soc Exp Biol Med. 220. 88-93 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takako Fujise,et al.: "Satiation and masticatory function modulated by brain histamine in rats." Proc Soc Exp Biol Med. 217. 228-234 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shuji Hidaka,et al.: "Molecular cloning of rat uncoupling 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats." Bioch Biophy Acta. 1389. 178-186 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toshiie Sakata,et al.: "Progress in Obesity Research 1998" Eds.by B.Guy-Grand & G.Aihoud,John Libbey (in press), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toshiie Sakata,et al.: "Molecular Approaches to Energy Metabolism" Eds.by H.Yamashita & S.Koizumi,Elsevier (in press), (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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