2007 Fiscal Year Final Research Report Summary
Regulation of the expression of adipocytokines and a novel therapeutic strategy for a metabolic syndrome
| Project/Area Number |
15081209
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
KOMURO Ryutaro Osaka University, Graduate School of Medicine, Assistant Professor (40403183)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Kazuhisa Osaka Universtity, Graduate School of Medicine, Assistant Professor (60397750)
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| Project Period (FY) |
2003 – 2007
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| Keywords | adiponectin / adiponectin promoter / Reactive Oxygen Species(ROS) / Catalase / Hypoxia / endoplasmic reticulum (ER) stress / RhoA / Nitrie Oxide(NO) |
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| Research Abstract |
Analysis of adiponectin promoter: We found an important element for the expression of adiponectin in the upstream from the initiation codon. We also found that Glimepiride could function as a direct ligand to PPAR_γ and increase the expression of adiponectin mRNA at transcriptional level. We cloned 11kb human adiponectin promoter which was more specific to adipocyte as compared to aP2 promoter.
Fat-derived reactive oxygen species (ROS): We found the upregulated gene expression of the enzymes involved in generating ROS and the downregulated gene expression of the enzymes involved in remov ing ROS in obese adipose tissue. Consequently, systemic ROS increased, adiponectin expression decreased, and the mRNA expression of proinflammatory cytokines increased. We also found that visceral fat accumulation in human were closely associated with systemic ROS level. We identified PPAR_γ-responsive element in the promoter of Catalase which we found important for obese adipose tissue.
Fat hypoxia: We found that obese adipose tissue was at hypoxic state with hypoperfusion of blood and ER stress was induced in adipocytes. Consequently, the expression of CHOP mRNA increased and the adiponectin mRNA expression was reduced at transcriptional level.
Fat Rho GTPases: The inhibition of RhoA-ROCK signaling pathway, which was crucial for physiologic al function of adipocyte and adipose tissue, increased the expression of adiponectin mRNA at transcriptional level.
Fat-derived NO: We found the increase of the expression of NO synthase mRNA and nitrosylated protein in obese adipose tissue. We also found that NO was involved in the regulation of adiponectin expression irrespectively of JNK or NFκB signaling pathway.
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Research Products
(21 results)
