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Transcriptional regulation of leptin in adipocytes.

Research Project

Project/Area Number 09671054
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OGAWA Yoshihiro  Kyoto University Graduate School of Medicine.Assistant Professor, 医学研究科, 助手 (70291424)

Co-Investigator(Kenkyū-buntansha) HOSODA Kiminori  Kyoto University Graduate School of Environmental studies.Assistant Professor, 人間環境学研究科, 助手 (40271598)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsLeptin / Transcriptional regulation / adipocytes / BeWo cells / Transfection / C / EBP alpha / Sp1 / 脂肪組織 / ゲルシフトアッセイ / プロモーター活性 / 肥満遺伝子 / 胎盤 / ルシフェラーゼ
Research Abstract

We examined the promoter activity of the human leptin 5'-flanking sequences in primary cultures of rat mature adipocytes and BeWo cells, a human trophoblast cell line. Various length of the human leptin 5'-flanking sequences were subcloned into the promoterless firefly luciferase expression vector. In rat mature adipocytes, the longest promoter (-2080 to + 108) construct showed a high-level transcription activity. When deletion proceeded from -2080 to -136, no significant changes in promoter activity were noted. This 136-bp region contained three Sp1 binding sites and a C/EBP binding site. When the Sp1 sites and C/EBP site were simultaneously mutated, the promoter activity was reduced to that of the promoterless construct. In BeWo cells, the longest promoter (-2080 to +108) construct also showed a high-level transcription activity. Deletion from -2080 to -1885 made no significant changes. However, the promoter activity was decreased by more than 80%, when sequences between -1885 and -1830 were deleted. Electrophoretic mobility shift assays revealed the presence of nuclear protein(s) binding to the sequences (-1885 to -1830) in BeWo cells but not in rat mature adipocytes. We also investigated the effect of protein kinases A and C on leptin production in adipocytes and BeWo cells. Leptin production was decreased by forskolin but unchanged by PMA.Leptin production in BeWo cells was increased by forskolin. The forskolin-induced increase in leptin production was completely suppressed by H89, an inhibitor of protein kinase A.Leptin production in BeWo cells was increased by phorbol myristate acetate (PMA). The PMA-induced increase in leptin production was completely suppressed by H7 and staurosporine, both of which are inhibitors of protein kinase C.The present study demonstrates that the human leptin gene transcription is differentially regulated between adipocytes and placental trophoblasts.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Masuzaki et al.: "Nonadipose tissue production of leptin : Leptin as a novel placenta-derived hormone in humans." Nature Med.3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Sagawa et al.: "Leptin production by hydatidiform mole." Lancet. 350. 1518-1519 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Ebihara et al.: "Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription." : Biochem.Biophys.Res.Commun.241. 658-663 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Yura et al.: "Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells." J.Clin.Endocrinol.Metab.83. 3609-3614 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Imagawa et al.: "Structure-function studies of human leptin." J.Biol.Chem.273. 35245-35249 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Ogawa et al.: "Leptin, a novel placenta-derived hormone in humans." Progress in Obesity Research. 8. 71-75 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Masuzaki, Y.Ogawa, N.Sagawa, K.Hosoda, T.Matsumoto, H.Mise, H.Nishimura, Y.Yoshimasa, I.Tanaka, T.Mori, and K.Nakao.: "Nonadipose tissue production of leptin : Leptin as a novel placenta-derived hormone in humans." Nature Med.3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Sagawa, T.Mori, H.Masuzaki, Y.Ogawa, and K.Nakao.: "Leptin production by hydatidiform mole." Lancet. 350. 1518-1519 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Ebihara, Y.Ogawa, N.Isse, K.Mori, N.Tamura, H.Masuzaki, K.Kohno, S.Yura, K.Hosoda, N.Sagawa, and K.Nakao.: "Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription." Biochem.Biophys.Res.Commun. 241. 658-663 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Yura, N.Sagawa, Y.Ogawa, H.Masuzaki, H.Mise, T.Matsumoto, K.Ebihara, S.Fujii, and K.Nakao.: "Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells." J.Clin.Endocrinol.Metab. 83. 3609-3614 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Imagawa, Y.Numata, G.Katsuura, I.Sakaguchi, A.Morita, S.Kikuoka, Y.Matsumoto, T.Tsuji, M.Tamaki, K.Sasakura, H.Teraoka, K.Hosoda, Y.Ogawa, and K.Nakao: "Structure-function studies of human leptin." J.Biol.Chem. 273. 35245-35249 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Ogawa, N.Sagawa, H.Masuzaki, S.Yura, H.Mise, K.Ebihara, S.Fujii, and K.Nakao.: "Leptin, a novel placenta-derived hormone in humans. Progress in Obesity Research : 8 edited by G.Ailhaud & B.Guy-Grand" John Libbey & Company Ltd.71-75 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hioko Mise et al.: "Augmented placental production of leptin in preeclampsia : Possible involvement of placental hypoxia." J.Clin.Endocrinol.Metab.83. 3225-3229 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigeo Yura et al.: "Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells." J.Clin.Endocrinol.Metab.83. 3609-3614 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Keiichi Imagawa et al.: "Structure-function studies of human leptin." J.Biol.Chem.273. 35245-35249 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Keiichi Imagawa et al.: "Development of a sensitive ELISA for human leptin using monoclonal antibodies." Clin.Chem.44. 2165-2171 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Noriko Satoh et al.: "Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system." Neurosci.Lett.249. 107-110 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshihiro Ogawa et al.: "Leptin,a novel placenta-derived hormone in humans." Progress in Obesity Research. 8. 71-75 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masuzaki et al.: "Nonadipose tissue production of leptin : Leptin as a novel placenta-derived hormone in humans." Nature Med.3. 1029-1033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sagawa et al.: "Leptin production by hydatidiform mole." Lancet. 350. 1518-1519 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ebihara et al.: "Identification of the human leptin 5′-flanking sequences involved in the trophoblast-specific transcription." Biochem.Biophys.Res.Commun.241. 658-663 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masuzaki et al.: "Glucocorticoid regulation of leptin synthesis and secretion in humans-Elevated plasma leptin levels in Cushing's syndrome-" J.Clin.Endocrinol.Metab.82. 2542-2548 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiraoka et al.: "Augmentation of obese(ob)gene expression and leptin secretion in obese spontaneously hypertensive rats(obese SHR or Koletsky rats)." Biochem.Biophys.Res.Commun.231. 582-585 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Satoh et al.: "Pathophysiologic significance of the obese gene product,leptin,in ventromedial hypothalamus(VMH)-lesioned rats -Evidence for loss of its satiety effect in VMH-lesioned rats-." Endocrinology. 138. 947-954 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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