| Project/Area Number |
21590756
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General internal medicine (including Psychosomatic medicine)
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
ETO Masato 東京大学, 医学部附属病院, 特任准教授 (80282630)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IIJIMA Katsuya 東京大学, 高齢社会総合研究機構, 准教授 (00334384)
OTA Hidetaka 東京大学, 医学部附属病院, 助教 (20431869)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | eNOS / 脂肪細胞 / 脂肪酸 / インスリン抵抗性 / メタボリック・シンドローム |
|---|
| Research Abstract |
Nonalcoholic steatohepatitis(NASH) is emerging as an independent risk factor for atherosclerotic cardiovascular disease associated with insulin resistance. However, pathogenesis of NASH is not fully elucidated. eNOS knock-out(KO) mice show metabolic consequences but the hepatic phenotype remain determined.
In this project, we found that only administration of high fat diet(HFD) could induce NASH in eNOS KO mice, not in wild type mice. eNOS was expressed in adipocytes and the inhibition of eNOS/NO enhanced lipolysis in vitro and in vivo. A PPAR gamma antagonist up-regulated the expression of eNOS in adipocytes and gave rise to the resistance to HFD induced fatty liver. Furthermore, reduction of eNOS expression in adipocytes by HFD was also prevented by the drug.
In conclusion, eNOS in adipocytes plays a preventive role in the pathogenesis of NASH through the inhibition of lipolysis. These findings could provide new insights into the therapeutic approach for NASH and atherosclerotic cardiovascular disease.
|
