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Identification of a novel secreted satiety protein that is activated by PPARγ activation

Research Project

Project/Area Number 15390291
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionGunma University

Principal Investigator

MORI M  Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80174382)

Co-Investigator(Kenkyū-buntansha) SHIMIZU H  Gunma University, Associate Professor, 医学部, 講師 (20251100)
YAMADA M  Gunma University, Associate Professor, 医学部, 講師 (90261833)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥9,500,000 (Direct Cost: ¥9,500,000)
KeywordsSatiety factor / PPARγ / Obesity / NAP / 食欲調節 / 脂肪細胞 / 視床下部 / N-associated protein
Research Abstract

We identified a protein of unknown function, termed NAP, that is expressed in the feeding-related hypothalamic nuclei and fat in rodents, using subtraction cloning analysis of PPARγ-activated cells. Icv injection of NAP caused a dose-dependent decrease in food intake, and icv injection of its antibody increased this. Expressions of NAP gene and protein in the lateral hypothalamic nuclei were significantly decreased in over-night starved rats. The hypothalamic NAP was co-localized with prohormone convertases, and the band corresponding to NAP-1 was observed in the rat brain extracts and cerebrospinal fluids. Icv injection of NAP-1, but not another regions of NAP, produced satiety, and an antibody recognizing NAP-1 oppositely elevated feeding behavior. Chronic icv injection of NAP-1 caused a significant decrease in both food intake and body weight. In contrast, an increased feeding and consequent obesity were found in rats receiving chronic icv administration of both antisense against NAP gene. Icv injection of NAP-1 significantly reduced food intake in fa/fa rats. Data presented here show that NAP functions satiety in the hypothalamus and that its administration is efficient in a condition of leptin resistance.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004 2003 Other

All Journal Article (22 results) Publications (4 results)

  • [Journal Article] Expression of type2 iodothryonine deiodinase in human osteoblast is stimulated by thyrotropin2005

    • Author(s)
      Morimura T
    • Journal Title

      Endocrinology 146

      Pages: 2077-2084

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thyrotropin - releasing hormone (TRH) Specific interaction between amino terminus of P-Lim and CREB binding protein (CBP)2005

    • Author(s)
      Hashimoto K
    • Journal Title

      Mol Cell Endocrinol 229

      Pages: 11-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4 containing vesicles, Identification of Akt2 specific substrate.2005

    • Author(s)
      Yamada E
    • Journal Title

      J Cell Biol 168

      Pages: 921-926

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aberrant dynamics of histone deacetylation at the thyrotropin-releasing hormone gene in resistance to thyroid hormone.2004

    • Author(s)
      Ishii S
    • Journal Title

      Mol Endocrinol 18

      Pages: 1708-1720

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF.2004

    • Author(s)
      Saito T
    • Journal Title

      Endocrinology 145

      Pages: 4232-4243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Allelic losses on chromosome 3p are accumulated in relation to morphological changes of lung adenocarcinoma2004

    • Author(s)
      Iijima H
    • Journal Title

      Brit J Cancer 91

      Pages: 1143-1148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fenofibrate, troglitazone, and 15-deoxy-δ^<12,14>-prostaglandin J_2 close KATP channels and induce insulin secretion.2004

    • Author(s)
      Shimomura K
    • Journal Title

      J Pharmacol Exp Therap 310

      Pages: 1273-1280

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 9HODE stimulates cell proliferation and extracellular matrix synthesis in human mesangial cells via PPAR gamma.2004

    • Author(s)
      Negishi M
    • Journal Title

      Exp Biol Med 229

      Pages: 1053-1060

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Allelic losses on chromosome 3P are accumulated in relation to morphological changes of lung adenocarcinoma.2004

    • Author(s)
      Iijima H
    • Journal Title

      Brit J Cancer 91

      Pages: 1143-1148

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinicopathological significance of aberrant methylation of RARβ2 at 3p24, RassF1aA at 3p213, and FHIT at 3p142 in patients with non-small cell lung cancer.2004

    • Author(s)
      Tomizawa Y
    • Journal Title

      Lung Cancer 46

      Pages: 305-312

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thyrotropin - releasing hormone(TRH) Specific interaction between amino terminus of P-Lim and CREB binding protein(CBP).2004

    • Author(s)
      Hashimoto K
    • Journal Title

      Mol Cell Endocrinol 229

      Pages: 11-20

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Two short segments of Smad 3 are important for specific interaction of Smad 3 with c-ski and snoN.2003

    • Author(s)
      Mizuide M
    • Journal Title

      J Biol Chem 278

      Pages: 531-536

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Troglitazone inhibits isolated cell proliferation, and induces apoptosis in isolated rat mesagial cells.2003

    • Author(s)
      Tsuchiya T
    • Journal Title

      American J Nephrol 23

      Pages: 222-228

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of type2 iodo thyronine deiodinase in corticotropin-secreting mouse pituitary tumor cells is stimulated by glucocorticoid...2003

    • Author(s)
      Araki O
    • Journal Title

      Endocrinology 144

      Pages: 4459-4465

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Syntaxin 4 and synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic beta HC-9cell.2003

    • Author(s)
      Saito T
    • Journal Title

      J Biol Chem 278

      Pages: 36718-36725

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Leucine at codon 428 in the minth heptad of thyroid hormone receptor beta 1 is necessary for interactions regardless of dimer formations2003

    • Author(s)
      Moden T
    • Journal Title

      Thyroid 13

      Pages: 427-435

    • Related Report
      2004 Annual Research Report
  • [Journal Article] C-Jun N-terminal Kinase negatively regulates lipopolysacharide-induced IL-12 production in human macrophages : role of mitogen-activated protein kinase in glutathione redox regulation of IL-12 production^12003

    • Author(s)
      Utsugi M
    • Journal Title

      J Immunol 171

      Pages: 628-635

    • Related Report
      2004 Annual Research Report
  • [Journal Article] C-Jun-NH_2-terminal kinase mediates expression of connective tissue growth factor induced by transforming growth factor-beta1 in human lung fibroblasts.2003

    • Author(s)
      Utsugi M
    • Journal Title

      American J Respir Cell Mol Biol 28

      Pages: 754-761

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Relationship between hyperinsulinemia and pulse wave velocity in moderately hyperglycemic patients.2003

    • Author(s)
      Koizumi M
    • Journal Title

      Diabetes Res Clinical Practice 62

      Pages: 17-21

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased activity and expression of phospholipase C2 in human colorectal cancer.2003

    • Author(s)
      Oshimoto H
    • Journal Title

      Oncology Res 14

      Pages: 31-37

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Probative approach for noninvasive evaluation of airway hyperresponsiveness and remodelingin adult asthwatics.2003

    • Author(s)
      Tsukagoshi H
    • Journal Title

      Lung 182

      Pages: 37-50

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21 in brain tumors.2003

    • Author(s)
      Horiguchi K
    • Journal Title

      Oncogene 22

      Pages: 7862-7865

    • Related Report
      2004 Annual Research Report
  • [Publications] Mizuide M, et al.: "Two short segments of smad 3 are important for specific interaction of smad 3 with c-ski and snoN."J Biol Chem. 278. 531-536 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchiya T, et al.: "Troglitazone inhibits isolated cell proliferation, and induces apoptosis in isolated rat mesangial cells."Am J Nephrol. 23. 222-228 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Areki O, et al.: "Expression of type 2 iodothyronine deiodinase in corticotropine-secreting mouse pituitary tumor cells is stimulated by glucocorticoid and Corticotropin-releasing hormone."Endocrinology. 144. 4459-4465 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Saito T, et al.: "Syntaxin 4 and synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic beta HC-9cell."J Biol Chem. 278. 36718-36725 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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