| Project/Area Number |
17590922
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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 Fukui |
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Principal Investigator |
TAKAHASHI Sadao University of Fukui, University of Fukui Hospital, Associate Professor (50303376)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Jinya University of Fukui, Faculty of Medical Sciences, Assistant Professor (20293417)
ZENIMARU Yasuo University of Fukui, Hospital, Medical Doctor (20397269)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | AMP Kinase / Lipoprotein Metabolism / Glucose Metabolism / Energy Metabolism / Cardiomyocyte / Skeletal Muscle cell / 心筋代謝 / 糖尿病 / リポ蛋白受容体 / 発現調節 |
|---|
| Research Abstract |
1. Sepsis accompanies myocardial dysfunction and dynamic alterations of cardiac metabolism. We have recently demonstrated that the very low-density lipoprotein receptor (VLDL-R), which is abundantly expressed in the heart, plays a key role in energy metabolism of the fasting heart. Electron microscopy and immunohistochemistry demonstrated that LPS significantly decreased both lipid accumulation and VLDL-R expression in the hearts of fasting mice. Treatment with LPS also downregulated VLDL-R in rat neonatal cardiac myocytes, and this downregulation was completely reversed by interleukin (IL)-1β receptor antagonist. IL-1β downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled h-VLDL but not DiI-labeled low-density lipoprotein (LDL). Use of specific pharmacologic inhibitors and short interference RNA revealed that Hsp90 was required for IL-1β to downregulate VLDL-R expression. These findings suggest that IL-1β is a princi
… More
ple mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression.
2. Glucose and fatty acids are major energy sources in skeletal muscle. VLDL-R is highly expressed in heart, skeletal muscle and adipose tissue, plays a crucial role in metabolism of triglyceride-rich lipoproteins. To explore energy switching between glucose and fatty acids, we studied expression of VLDL-R and lipoprotein uptake in rat L6 myoblasts. L-glucose or D-glucose deprivation in the medium noticeably induced the AMPK activation and VLDL-R expression. Dose-dependent induction of VLDL-R expression was observed when D-glucose was less than 4.2 mM. The same phenomenon was also observed in rat primary, skeletal myoblasts and cultured vascular smooth muscle cells. The uptake of β-VLDL but not LDL was accompanied by induction of VLDL-R expression. These findings suggest that the VLDL-R-mediated uptake of triglyceride-rich lipoproteins might compensate for glucose shortfall through AMPK activation in skeletal muscle. Less
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