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Studies on a model animal for atherogenic lipoproteins and atherosclerosis

Research Project

Project/Area Number 13671172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHIMAO Hitoshi  University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 講師 (20251241)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Akimitsu  University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 助手 (70344893)
SONE Hrohito  University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 講師 (30312846)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsatherosclerosis / lipoproteins / remnant lipoproteins / LDL / mice / triglycerides / SREBO / SREBP / コレステロール
Research Abstract

To investigate effects of enhanced hepatic trigylcerides synthesis on production of atherogenic lipoproteins, SREBP-lc transgeni and LDL receptor-deficient doubly mutant mice (BP1c/LDLRKO). were generated and their plasma lipoproteins were studied BP1c/LDLRKO showed incrases in plasma triglycerides and cholesterol especially at feeding. On agarose electrophoresis, broa beta band, suggesting presence of remnant lipoproteins was increased and LIDL cholesterol was inversely decreased as compared to controls of LDLR KO mice. Northern blot analysis of livers showed that over-expression of SREBP-lc induced expression of lipogenic enzyme genes such as FAS, ACC, and SCO. Activation of lipogenic gene expression could incrase hepatic postprandia synthesis of triglycerides and production of TG rich lipoproteins, which were accumulated in the absence of LDLR converting to remnant lipoproteins in plasma. Due to the accumulation of these atherogenic lipoproteins, BP1c/LDLRKO exhibited atherorm formation around aortic sinus at age of 8 months even on a regular diet. These mice are a good model for postprandial hyperlipidemia and metabolic syndrome.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Hasty AH: "Severe Hypercholesterolemia, Hypertriglyceridemia and Atherosclerosis in mice Lacking Both Leptin and the Low Density Lipoprotein Receptor"J Biol Chem. 276. 37402-37408 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sone H: "Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Protein-1."Am J Physiol Endocrinol.Metab. 282・1. E222-E230 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T: "Polyunsaturated fatty acids suppress sterol regulatory element-binding protein-1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements."J.Biol.Chem. 277・3. 1705-1711 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yahagi N: "Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers, but not obesity or insulin resistance in Lepob/Lepob mice."J Biol Chem. 277・22. 19353-19357 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Amemiya-Kudo M: "Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes."J Lipid Res. 43・8. 1220-1235 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaka T: "Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs."J Lipid Res. 43・6. 911-920 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T: "Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling."Mol Endocrinol. 17・7. 1240-1254 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ide T: "Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling."Mol Endocrinol. 17・7. 1255-1267 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yahagi N: "p53 Activation in adipocytes of obese mice."J Biol Chem. 278・28. 25395-25400 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sekiya M: "Polyunsaturated fatty acids decrease fat storage in livers of obese mice by SREBP-1 suppression."Hepatology. 38・6. 1529-1539 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasty AH et al.: "Severe Hypercholesterolemia, Hypertriglyceridemla and Atherosclerosis in mice Lacking Both Leptin and the Low Density Lipoprotein Receptor"J Biol Chem. 276. 37402-37408 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sohe H et al.: "Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Protein-1."Am J Physiol Endocrinol.Metab.. 282(1). E222-E230 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T. et al.: "Polyunsaturated fatty acids suppress sterol regulatory element-binding protein-1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements."J.Biol.Chem. 277(3). 1705-1711 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yahagi N et al.: "Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers, but 'not obesity or insulin resistance in Lepob/Lepob mice."J Biol Chem.. 277(22). 19353-19357 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Amemiya-Kudo M, et al.: "Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes."J Lipid Res.. 43(8). 1220-1235 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaka T, et al.: "Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs."J Lipid Res.. 43(6). 911-920 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T et al.: "Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism.I.PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling."Mol Endocrinol.. 17(7). 1240-1254 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ide T et al.: "Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism.II.LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling"Mol Endocrinol.. 17(8). 1266-1267 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yahagi N et al.: "p53 Activationin adipocytes of obese mice."J Biol Chem.. 278(28). 25395-25400 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sekiya M, et al.: "Polyunsaturated fatty acids decrease fat storage in livers of obese mice by SREBP-1 suppression."Hepatology. 38/6. 1529-1539 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasty AH: "Severe Hypercholesterolemia, Hypertriglyceridemia, and Atherosclerosis in mice Lacking Both Leptin and the Low Density Lipoprotein Receptor"J Biol Chem.. 276. 37402-37408 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sone H: "Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Protein-1"Am J Physiol Endocrinol. Metab.. 282(1). E222-230 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T: "Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements"J. Biol. Chem.. 277(3). 1705-1711 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yahagi N: "Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers, but not obesity or insulin resistance in Lepob/Lepob mice"J Biol Chem.. 31;277(22). 19353-19357 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Amemiya-Kudo M: "Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes"J Lipid Res.. 43(8). 1220-1235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuzaka T: "Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs"J Lipid Res.. 43(6). 911-920 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hasty AH.: "Severe Hypercholesterolemia, Hypertriglyceridemia and Atherosclerosis in mice Lacking Both Leptin and the Low Density Lipoprotein Receptor"J Biol Chem. 276. 37402-37408 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshikawa T.: "Identification of LXR/RXR as an Activator of the Sterol Regulatory Element-Binding Protein(SREBP)-1c Gene Promoter"Mol Cell Biol. 21. 2991-3000 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakakura Y.: "Sterol Regulatory Element-Binding Proteins Induce an Entire Pathway of Cholesterol Synthesis"Biochem Biophys Res Commun. 286(1). 176-183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sone H.: "Acety1-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Protein-1"Am J Physiol Endocrinol. Metab.. 282(1). E222-230 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuzaka T.: "Dual regulation of mouse delta-5 and-6 desaturase gene expression by SREBP-1 and PPARa"J. Lipid. Res.. 43(1). 107-114 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshikawa T.: "Polyunsaturated fatty acids suppress sterol regulatory element-binding protein-1c promoter activity by inhibition of liver X receptor(LXR)binding to LXR respons elements"J. Biol. Chem. 277(3). 1705-1711 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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