2007 Fiscal Year Final Research Report Summary
Elucidation of the regulatory mechanism of very low-density lipoprotein (VLDL) reeptor expression by glucose metabolism
| 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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| Keywords | AMP Kinase / Lipoprotein Metabolism / Glucose Metabolism / Energy Metabolism / Cardiomyocyte / Skeletal Muscle cell |
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| 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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[Journal Article] Glucose deprivation accelerates VLDL receptor-mediated TG-rich lipoprotein uptake by AMPK activation in skeletal muscle cells2008
Author(s)
Zen, imaru, Y., Takahashi, S., Takahashi, M., Yamada, K., Iwasaki, T., Hattori, H., Imagawa, M., Ueno, M., Suzuki, J., Miyamori, I
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Journal Title
Biochem. Biophys 368
Pages: 716-722
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Changes in cardiac lipid metabolism during sepsis : The essential role of very low-density lipoprotein receptors2006
Author(s)
Jia, L., Takahashi, M., Morimoto, H., Takahashi, S., Izawa, A., Ise, H., Iwasaki, T., Hattori, H., Wu, K. J., Ikeda, U
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Journal Title
Cardiovas 69
Pages: 545-555
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Low glucose accelerates VLDL receptor-mediated lipoprotein uptake in skeletal muscle cells2007
Author(s)
Zenimaru, Y., Takahashi, S., Imagawa, M., Suzuki, J., Miyamori, I
Organizer
67th Scientific section, American American Diabetes Association
Place of Presentation
Chicago USA
Year and Date
2007-06-24
Description
「研究成果報告書概要(欧文)」より
