Elucidation of the association between non alcoholic steatohepatitis and endoplasmic reticulum stress by metabolomics of portal blood
| Project/Area Number |
16K09336
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
KAKAZU EIJI 東北大学, 東北大学病院, 助教 (20509377)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小暮 高之 東北大学, 医学系研究科, 非常勤講師 (70400330)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 遊離アミノ酸 / 非アルコール性脂肪性肝炎 / 非アルコール性脂肪性肝疾患 / NAFLD / 門脈血 / アミノ酸 / 脂肪肝 / 3D培養 / 潅流培養 / 肝細胞 / パルミチン酸 / オレイン酸 / 小胞体ストレス / 門脈 |
|---|
| Outline of Final Research Achievements |
The aim of this study is to elucidate the association between the imbalance of free amino acids (FAAs) in portal blood (PB) and the pathogenesis of hepatic steatosis in NAFLD. We measured metabolites in PB of fasting WT mice and NAFLD model mice. Then, we made two media that were consistent with the levels of FAAs in the PB of wt or NAFLD model mice. We found that the decrease of 7 FAAs, especially Met and Tyr, in the media induced TG accumulation and ER stress via the suppression of lipid secretion from hepatocytes. The high fat, L-methionine (Met) / L-tyrosine (Tyr) -deficient diet (HF-MTD) induced steatosis and ballooning pathologically in the liver of C57BL/6 mice, but the HF diet did not.
|
| Academic Significance and Societal Importance of the Research Achievements |
これまで非アルコール性脂肪性肝炎（NASH)の環境要因として過剰な糖質、脂質の関与は多くの研究で証明されてきたが、本研究で一部の遊離アミノ酸の不均衡も肝細胞脂肪変性を悪化させNASHの要因となる可能性が示唆された。また、本研究で開発した門脈血類似潅流培養は生体内の環境に近い培養法で、肝細胞の代謝研究を行う上で従来の培養法よりもはるかに優れていると考える。今後、更に研究を発展させることで候補アミノ酸の代謝を促進することでNASHの治療・予防につながる可能性がある。
|
Report
(4 results)
Research Products
(12 results)
-
[Journal Article] The profiling of plasma free amino acids and the relationship between serum albumin and plasma-branched chain amino acids in chronic liver disease: a single-center retrospective study.2018
Author(s)
Akitoshi Sano, Eiji Kakazu, Tatsuki Morosawa, Jun Inoue, Takayuki Kogure, Masashi Ninomiya, Tomoaki Iwata, Teruyuki Umetsu, Takuya Nakamura, Satoshi Takai, Tooru Shimosegawa
-
Journal Title
Journal of Gastroenterology
Volume: 印刷中
Issue: 8
Pages: 978-988
DOI
Related Report
Peer Reviewed
-
-
-
-
-
[Presentation] The relationship between the plasma free amino acids and the pathological features in nonalcoholic fatty liver disease (NAFLD).2017
Author(s)
Eiji Kakazu, Akitoshi Sano, Tatsuki Morosawa, Jun Inoue, Takayuki Kogure, Masashi Ninomiya, Tomoaki Iwata, Teruyuki Umetsu, Takuya Nakamura, Satoshi Takai, Tooru Shimosegawa
Organizer
アメリカ肝臓学会 annual meeting
Related Report
Int'l Joint Research
-
-
-
-
-
-
