The effects of partial disruption of tricarboxylic acid cycle on energy metabolism. The analysis of expression forms of citrate synthetase gene-disrupted mice
| Project/Area Number |
16590864
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
SONE Hirohito University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (30312846)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMANO Hitoshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (20251241)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | tricarboxylic acid (TCA) cycle / citrate synthase / knockout mice / lifestyle-related disorders / KOマウス / エネルギー代謝 |
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| Research Abstract |
To find out solution over lifestyle-related metabolic disorders like obesity, diabetes and dyslipidemia, it is necessary to re-evaluate the significance of tricarboxylic acid (TCA) cycle, an important metabolic pathway with very high efficiency. To investigate the effects of inhibiting the cycle, the gene encoding citrate synthase (CS), one of rate-limiting enzymes of the cycle, was disrupted in mice. Homozygous (CS-/-) mice showed early embryonic lethality but heterozygous mice (CS+/-) showed partial expression of the CS gene in each of the mRNA, protein, and enzyme activity levels. Whereas there were no differences in weight, basal metabolic rate, blood pressure, fasting plasma glucose/insulin levels, serum lipid levels between wild-type and CS+/- mice, it is clarified that respiratory quotient (respiratory exchange ratio) was significantly lower and serum acetoacetate levels were significantly higher in CS+/- mice. High-fat high-sugar diet of one or two months for both wild-type and CS+/- mice resulted in marked blunted plasma response after intravenous glucose load without any differences in glucose responses in CS+/- mice compared with wild-type mice. It is thought that the mouse could be a useful model to investigate the mechanisms of insulin resistance underlying energy metabolism disorders.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes.2006
Author(s)
Nakagawa Y, Shimano H, Yoshikawa T, Ide T, Tamura M, Furusawa M, Yamamoto T, Inoue N, Matsuzaka T, Takahashi A, Hasty AH, Suzuki H, Sone H, Toyoshima H, Yahagi N, Yamada N.
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Journal Title
Nat Med. 12
Pages: 107-113
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients than the existing definitions. Additional analysis from the Japan Diabetes Complications Study.2006
Author(s)
Sone H, Tanaka S, Ishibashi S, Yamasaki Y, Oikawa S, Ito H, Saito Y, Ohashi Y, Akanuma Y, Yamada N, Japan Diabetes Complications Study (JDCS) Group.
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Journal Title
Diabetes Care 29
Pages: 145-147
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes2005
Author(s)
Takahashi A, Shimano H, Nakagawa Y, Yamamoto T, Motomura K, Matsuzaka T, Sone H, Suzuki H, Toyoshima H, Yamada N.
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Journal Title
Biochim Biophys Acta 1740
Pages: 427-433
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transgenic mice overexpressing nuclear SREBP-1c in pancreatic beta-cells.2005
Author(s)
Takahashi A, Motomura K, Kato T, Yoshikawa T, Nakagawa Y, Yahagi N, Sone H, Suzuki H, Toyoshima H, Yamada N, Shimano H.
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Journal Title
Diabetes 54
Pages: 492-499
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Statins downregulate ATP binding cassette transporter Al gene expression in macrophages.2004
Author(s)
Sone H, Shimano H, Shu M, Nakakuki M, Takahashi A, Sakai M, Sakamoto Y, Yokoo T, Matsuzaka K, Okazaki H, Nakagawa Y, Iida KT, Suzuki H, Toyoshima H, Horiuchi S, Yamada N.
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Journal Title
Biochem Biophys Res Commun 316
Pages: 790-794
Description
「研究成果報告書概要(欧文)」より
Related Report
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