Elucidation of the organ linkage between non-alcoholic steatohepatitis and cardiovascular disease mediated by the liver X receptor
| Project/Area Number |
18K10993
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 59040:Nutrition science and health science-related
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
林 由美 名古屋大学, 医学系研究科(保健), 講師 (30632707)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | NASH / 動脈硬化 / SHRSP5 / 心筋梗塞 / 胆汁酸 / 肝臓X受容体 / 非アルコール性脂肪性肝炎 |
|---|
| Outline of Final Research Achievements |
Liver X receptor (LXR) activity is expected to have an innovative effect of extracting cholesterol from once formed atherosclerotic lesions and regressing arteriosclerosis, but it also induces a lipid synthesis system gene (SREBP1c). It has the drawback of further exacerbating hepatic lipid deposition. In this study, in order to overcome this drawback, the applicants have a special purpose (1): the inhibitory effect of bile acid on SREBP1c activity and the purpose (2): the efficacy of vabagenin, which is a novel ligand candidate for LXR activity that does not activate SREBP1c. As a result of examination using the NASH- myocardial infarction onset model (SHRSP5 / Dmcr rat), the lipid deposition in the arteries was improved without aggravating fatty liver.
|
| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪性肝炎(NASH)は、大きな自覚症状がないことから長年軽視されてきた。しかしながら、NASHが肝硬変、肝がんに移行することが明らかとなったことで、積極的な治療ターゲットという認識に変わってきた。また、NASHは肝臓だけにとどまらず、メタボリックシンドロームを背景とした糖尿病、脂質異常症、高血圧を悪化させ、虚血性心疾患の発症率と死亡率を2倍以上高くすることも、予後を悪くする原因となっている。増大する医療費を削減するため、自覚症状が少ない早期のNASHのうちから、積極的な治療介入を行うことができれば、致死的な虚血性心疾患への進行を事前に食い止めることができる。
|
Report
(5 results)
Research Products
(19 results)
-
-
[Journal Article] Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial mesenchymal transition2021
Author(s)
Omer Faruk Hatipoglu, Eyyup Uctepe, Gabriel Opoku, Hidenori Wake, Kentaro Ikemura, Takashi Ohtsuki, Junko Inagaki, Mehmet Gunduz, Esra Gunduz, Shogo Watanabe, Takashi Nishinaka, Hideo Takahashi, Satoshi Hirohata
-
Journal Title
Biomedicine & Pharmacotherapy
Volume: 139
Pages: 111633-111633
NAID
Related Report
Peer Reviewed
-
-
[Journal Article] Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model2020
Author(s)
Shusei Yamamoto, Ikumi Sato, Natsuki Fukuhama, Natsumi Akiyama, Miku Sakai, Shota Kumazaki, Shang Ran, Satoshi Hirohata, Kazuya Kitamori, Yukio Yamori, Shogo Watanabe
-
Journal Title
Experimental and Molecular Pathology
Volume: in press
Related Report
Peer Reviewed
-
-
[Journal Article] Bile acid metabolism is an intermediary factor between non-alcoholic steatohepatitis and ischemic heart disease in SHRSP5/Dmcr rats2019
Author(s)
Shota Kumazaki, Mayu Nakamura, Shun Sasaki, Rina Tagashira, Nozomi Maruyama, Ikumi Sato, Shusei Yamamoto, Shang Ran, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Kazuya Kitamori, Mari Mori, Yukio Yamori, Shogo Watanabe
-
Journal Title
Journal of Nutrition and Food Sciences
Volume: 9(4)
Pages: 1-9
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
