Regulation and expression of lipid-metabolizing enzymes in muscle
Project/Area Number |
15580099
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Food science
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Research Institution | Ehime University (2004) Tohoku University (2003) |
Principal Investigator |
FUJINO Takahiro Ehime University, Integrated Center for Sciences, Associate Professor, 総合科学研究支援センター, 助教授 (40292312)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | starvation / lipid metabolism / skeletal muscle / glucose / transgenic mouse / transcriptional regulation / ストレス応答 / グルコース飢餓 |
Research Abstract |
Our project is to define the transcriptional regulation of genes involved in lipid metabolism of skeletal and cardiac muscle during fasting. AceCS2 is highly expressed in the cardiac and skeletal muscle and a marked induction of AceCS2 mRNA is seen in the heart and skeletal muscle when animals are fasted. We revealed that the induction of the mRNA in the skeletal muscle is largely contributed by a unique transcriptional factor, KLF15, a Kruppel-like factor and a combination of KLF15 and Sp1 resulted in a synergistic transcriptional activation of the AceCS2 gene. Furthermore, KLF15 overexpression induces the levels of AceCS2 transcripts both in myoblasts and in myotubes. KLF15 also regulates GLUT4 gene expression in both adipose and muscle cells. These data indicate that KLF15 may play important roles of the activation of genes involved in lipid metabolism of skeletal and cardiac muscle during fasting. AceCS2 is expressed in peripheral tissues including the cardiac and skeletal muscle but not in the liver. This expression pattern is similar to that of the rate-limiting enzyme for ketone body metabolism, succinyl-CoA ; 3-oxoacid, CoA transferase. To address why these enzyme is not expressed in the liver, we generated the transgenic mice highly expressing AceCS2 in the liver. We obtained six lines of AceCS2 transgenic mice, which were identified by Southern blotting and PCR, but could not find out any differences of the levels of serum glucose and cholesterol after 15h fasting.
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Report
(3 results)
Research Products
(12 results)