Regulation of the expression of adipocytokines and a novel therapeutic strategy for a metabolic syndrome
Grant-in-Aid for Scientific Research on Priority Areas
|Allocation Type||Single-year Grants|
|Research Institution||Osaka University|
KOMURO Ryutaro(2005-2007) Osaka University, Graduate School of Medicine, Assistant Professor (40403183)
下村 伊一郎(2003-2005) 阪大, 教授 (60346145)
MAEDA Kazuhisa Osaka Universtity, Graduate School of Medicine, Assistant Professor (60397750)
槇島 誠 日本大学, 医学部, 教授 (70346146)
|Project Period (FY)
2003 – 2007
Completed(Fiscal Year 2007)
|Budget Amount *help
¥111,900,000 (Direct Cost : ¥111,900,000)
Fiscal Year 2007 : ¥17,700,000 (Direct Cost : ¥17,700,000)
Fiscal Year 2006 : ¥17,700,000 (Direct Cost : ¥17,700,000)
Fiscal Year 2005 : ¥25,500,000 (Direct Cost : ¥25,500,000)
Fiscal Year 2004 : ¥25,500,000 (Direct Cost : ¥25,500,000)
Fiscal Year 2003 : ¥25,500,000 (Direct Cost : ¥25,500,000)
|Keywords||adiponectin / adiponectin promoter / Reactive Oxygen Species(ROS) / Catalase / Hypoxia / endoplasmic reticulum (ER) stress / RhoA / Nitrie Oxide(NO) / ピオグリタゾン / 脂肪細胞 / 肥満 / Rhoキナーゼ / PPARγ / PTEN / ミトコンドリア / エネルギー消費 / アディポサイトカイン / LRH-1 / 転写因子 / 転写共役因子|
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.
Research Products (30results)