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2004 Fiscal Year Final Research Report Summary

Relationship between the mechanism for hyperlipidemia and intestinal polyp formation in Apc knockout mice

Research Project

Project/Area Number 15590360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational Cancer Center

Principal Investigator

TAKAHASHI Mami  Natl.Cancer Ctr.Res.Inst., Cancer Prev.Basic Res., Proj., がん予防基礎研究プロジェクト, 室長 (90214973)

Project Period (FY) 2003 – 2004
KeywordsApc knockoutmouse / Hyperlipidemia / Intestinalpolyp / Lipoprotein lipase / Triglyceride / PPARα / PPARγ / Pioglitazone
Research Abstract

An age-dependent hyperlipidemic state in Ape-deficient mice was shown, and involvement of hyperlipidemia in intestinal polyp formation was examined using anti-hyperlipidemic agents. It was demonstrated that levels of serum triglycerides(TG) in Apc-deficient mice were markedly increased at 15-20 weeks of age. Then, the effects of a PPAR alpha ligand, bezafibrate, and a PPAR gamma ligand, pioglitazone, on both hyperlipidemia and intestinal polyp development in Apc-deficient mice, Apc^<1309> mice, were examined. Treatment of Apc^<1309> mice with 100 and 200 ppm pioglitazone or bezafibrate for 6 weeks from 6 weeks of age caused dose-dependent reduction in serum TG, along with a decrease in the numbers of intestinal polyps. When Min mice were treated with 100-1600 ppm pioglitazone for 14 weeks, a decrease of serum TG and polyp numbers was similarly observed to 7% and 9% of the untreated values, respectively, at the highest dose. Moreover, lipoprotein lipase(LPL) mRNA levels in the liver and small intestine of Apc^<1309> and Min mice were up-regulated by treatment with pioglitazone. Thus, the present study demonstrated that 100-1,600 ppm of pioglitazone can suppress both hyperlipidemia and polyp formation in Apc gene-deficient mice, so this PPAR gamma ligand might be a good candidate chemopreventive agent for colon cancer. In addition, it was shown that a LPL-selective activator, NO-1886,also suppressed both serum lipid levels and polyp formation in Min mice, suggesting that lowered activity of LPL in Apc-deficient mice may contribute to hyperlipidemia and polyp formation. These anti-hyperlipidemic agents might be good candidate chemopreventive agents for colon cancer.

  • Research Products

    (6 results)

All 2005 2003

All Journal Article (6 results)

  • [Journal Article] Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886, increasing lipoprotein lipase activity in Min mice.2005

    • Author(s)
      Niho, N. et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 2970-2974

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886,increasing lipoprotein lipase activity in Min mice.2005

    • Author(s)
      Niho, N., et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol.102

      Pages: 2970-2974

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc deficient mice by PPAR ligands.2003

    • Author(s)
      Niho, N., et al.
    • Journal Title

      Cancer Res. 63

      Pages: 6090-6095

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPARg ligand.2003

    • Author(s)
      Niho, N., et al.
    • Journal Title

      Cancer Sci. 94

      Pages: 960-964

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Concomitant suppression of hyperlipidemia and intestinal polyp formation in Ape deficient mice by PPAR ligands.2003

    • Author(s)
      Niho, N., et al.
    • Journal Title

      Cancer Res. Vol.63

      Pages: 6090-6095

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, α PPARg ligand.2003

    • Author(s)
      Niho, N., et al.
    • Journal Title

      Cancer Sci. Vol.94

      Pages: 960-964

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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