The therapeutic application of lipolytic machinery to obesity and its related disorders
| Project/Area Number |
15590930
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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 | The University of Tokyo |
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Principal Investigator |
OSUGA Jun-ichi The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (10334400)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Ken The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (40376463)
YAHAGI Naoya The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
TAMURA Yoshiaki The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
OKAZAKI Hiroaki The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | lipase / adipocyte / obesity / ホルモン感受性リパーゼ / トリグリセリド |
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| Research Abstract |
Hormone-sensitive lipase (HSL) plays a crucial role in the hydrolysis of triacylglycerol (TG) and cholesteryl ester in various tissues including adipose tissues. To explore the role of HSL in the metabolism of fat and carbohydrate, we have generated mice lacking both leptin and HSL (Lep^<ob/ob>/HSL^<-1->) by crossbreeding HSL^<-/-> mice with genetically obese Lep^<ob/ob> mice. Unexpectedly, Lep^<ob/ob>/HSL^<-/-> mice ate less food, gained less weight and had lower adiposity than Lep^<ob/ob>/HSL^<+/+> mice. Lep^<ob/ob>/HSL^<-/-> mice had massive accumulation of preadipocytes in white adipose tissues (WAT) with increased expression of preadipocyte-specific genes (C/EBPβ and ADRP) and decreased expression of genes characteristic of mature adipocytes (C/EBPα, PPARγ and ADD-1/SREBP-1). Consistent with the reduced food intake, hypothalamic expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) was decreased. Since HSL is expressed in hypothalamus, we speculate that defective generation of free fatty acids in the hypothalamus due to the absence of HSL mediates the altered expression of these orexigenic neuropeptides. Thus deficiency of both leptin and HSL has unmasked novel roles of HSL in adipogenesis as well as in feeding behavior.
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice.2004
Author(s)
Sekiya M, Osuga J, Okazaki H, Yahagi N, Harada K, Shen WJ, Tamura Y, Tomita S, Iizuka Y, Ohashi K, Okazaki M, Sata M, Nagai R, Fujita T, Shimano H, Kraemer FB, Yamada N, Ishibashi S.
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Journal Title
J Biol Chem 279
Pages: 15084-15090
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] p53 involvement in the pathogenesis of fatty liver disease.2004
Author(s)
Yahagi N, Shimano H, Matsuzaka T, Sekiya M, Najima Y, Okazaki S, Okazaki H, Tamura Y, Iizuka Y, Inoue N, Nakagawa Y, Takeuchi Y, Ohashi K, Harada K, Gotoda T, Nagai R, Kadowaki T, Ishibashi S, Osuga J, Yamada N.
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Journal Title
J Biol Chem 279
Pages: 20571-20575
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide.2004
Author(s)
Tamura Y, Osuga J, Adachi H, Tozawa R, Takanezawa Y, Ohashi K, Yahagi N, Sekiya M, Okazaki H, Tomita S, Iizuka Y, Koizumi H, Inaba T, Yagyu H, Kamada N, Suzuki H, Shimano H, Kadowaki T, Tsujimoto M, Arai H, Yamada N, Ishibashi S.
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Journal Title
J Biol Chem 279
Pages: 30938-30944
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene.2003
Author(s)
Ohashi K, Osuga J, Tozawa R, Kitamine T, Yagyu H, Sekiya M, Tomita S, Okazaki H, Tamura Y, Yahagi N, Iizuka Y, Harada K, Gotoda T, Shimano H, Yamada N, Ishibashi S.
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Journal Title
J Biol Chem 278
Pages: 42936-42941
Description
「研究成果報告書概要(欧文)」より
Related Report
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