The involvment of vagus nerve on the pathogenesis of NASH
Project/Area Number |
17K09442
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Aichi Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
角田 圭雄 愛知医科大学, 医学部, 准教授 (10636971)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | NASH / 迷走神経 / 高脂肪食 / 肝脂質代謝 / 求心性線維 / NAFLD / CD36 / カプサイシン / NMDA受容体 |
Outline of Final Research Achievements |
To investigate the effect of hepatic branch of vagus nerve transection (HV) on nonalcoholic steatohepatitis (NASH), 6-week-old male BALB/C mice were subjected to HV and sham surgery and then fed a high fat diet (HFD). It continued until the 18th week after the commencement of HFD. HFD-induced fatty liver was decreased in HV group compared to sham group. Vagal afferent fibers denervation reduced HFD-induced fatty liver, and hepatic fat was reduced by using an antagonist to the N-methyl-D-aspartate (NMDA) receptor present in the dorsal nucleus of the vagus nerve. These results suggest that NASH-induced hepatic steatosis may involve vagal afferent fibers and vagal dorsal nucleus pathways.
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Academic Significance and Societal Importance of the Research Achievements |
これまでに迷走神経を介して特殊飼料や特定の遺伝子KOマウスを用いたNASHモデルにおいて脂肪性肝炎を促進するといった報告があった。一方で迷走神経刺激はnicotinic α7受容体を介して抗炎症作用を有するという報告があり、NASHにおける役割についてはっきりしなかった。本研究でマウスにおいて高脂肪食によるNASHの肝脂肪化に迷走神経求心性線維および延髄迷走神経背側核を介していることが明らかになった。一方でNASHにおける肝炎症および肝線維化に迷走神経は保護的に作用する可能性があることも明らかとなり、NASHの病態に迷走神経が関与している可能性がある意義深い研究と考えられた。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Conophylline inhibits high fat diet-induced non-alcoholic fatty liver disease in mice2018
Author(s)
T. Ohashi, Y. Nakade, M. Ibusuki, R Kitano, T. Yamauchi, S. Kimoto, T. Inoue, Y. Kobayashi, N. Ishii, Y. Sumida, K. Ito, H. Nakao, K. Umezawa, M. Yoneda
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Journal Title
PLOS One
Volume: electronic
Issue: 1
Pages: e0210068-e0210068
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Delta40p53 suppresses tumor cell proliferation and induces cellular senescence in hepatocellular carcinoma cells2017
Author(s)
Ota A, Nakao H, Sawada Y, Karnan S, Wahiduzzaman M, Inoue T, Kobayashi Y, Yamamoto T, Ishii N, Ohashi T, Nakade Y, Sato K, Itoh K, Konishi H, Hosokawa Y, Yoneda M
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Journal Title
J Cell Sci
Volume: 130
Issue: 3
Pages: 614-625
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Conophylline inhibits non-alcoholic steatohepatitis in mice2017
Author(s)
Nakade Yukiomi、Sakamoto Kazumasa、Yamauchi Taeko、Inoue Tadahisa、Kobayashi Yuji、Yamamoto Takaya、Ishii Norimitsu、Ohashi Tomohiko、Sumida Yoshio、Ito Kiyoaki、Nakao Haruhisa、Fukuzawa Yoshitaka、Umezawa Kazuo、Yoneda Masashi
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Journal Title
PLOS ONE
Volume: 12
Issue: 6
Pages: e0178436-e0178436
DOI
Related Report
Peer Reviewed / Open Access
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