| Project/Area Number |
18390230
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MANABE Ichiro The University of Tokyo, Graduate School of Medicine, Project Lecturer (70359628)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Ryozo The University of Tokyo, Hospital, Professor (60207975)
NISHIMURA Go The University of Tokyo, Hospital, Intern Doctor (20422305)
FUJIU Katsuhito The University of Tokyo, Hospital, Research Associate (30422306)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,730,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | Cardiovascular disease / Diabetes mellitus / Translational research / Atherosclerosis / Metabolic syndrome / Transcriptional regulation / KLF5 |
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| Research Abstract |
Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. In this project we analyzed the roles played by Kruppel-like transcription factor 5 (KLF5) in metabolic syndrome and cardiovascular disease. KLF5 heterozygous knockout (KLF5^<+/->) mice were resistant to high-fat-induced obesity, hypercholesterolemia, glucose intolerance and hepatic steatosis, despite consuming more food than wild-type mice. This may in part reflect their increased systemic O_2 consumption, indicating enhanced energy expenditure. Expression of the genes involved in lipid oxidation and energy uncoupling was upregulated in the soleus muscles of KLF5^<+/-> mice and in C2Cl2 myotubes in which KLF5 was knocked down. We demonstrated that KLF5 is a crucial regulator of energy metabolism. KLF5 acts with PPARδ to play a central role in transcriptional regulatory programs governing expression of genes related to fatty acid catabolism. KLF5 interacts with RAR in smooth muscle cells and the differences in interacting partners in different tissues appear to determine tissue-specific functions of KLF5.
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