Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A

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Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A

Persistent ID (NDL): info:ndljp/pid/12970409

Material type: 博士論文

Author: Owaki, Takashi

Publisher: -

Publication date: 2023-03-23

Material Format: Digital

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Name of awarding university/degree: 新潟大学,博士（医学）

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Note (General)：: Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism of action in autonomic neural signal pathways ...

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Material Type: 博士論文
Title: Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A
Author/Editor: Owaki, Takashi
Author Heading: Owaki, Takashi
Publication Date: 2023-03-23
Publication Date (W3CDTF): 2023-03-23
Alternative Title: 非アルコール性脂肪性肝疾患の病態に肝臓と腸を連関する自律神経経路が肝臓セロトニン受容体2Aを介して関与する
Degree grantor/type: 新潟大学
Date Granted: 2023-03-23
Date Granted (W3CDTF): 2023-03-23
Dissertation Number: 甲第5114号
Degree Type: 博士（医学）
Text Language Code: eng
Alias of Author: 大脇, 崇史
Subject Heading: Fatty liver
Autonomic neuron
5-HT
Antagonist
Brain
Target Audience: 一般
Note (General): Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism of action in autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor (MC4R) knockout (MC4RKO) mice, and the effects of the autonomic neural axis on NAFLD physiology, 5-HT and its receptors (HTRs), and lipid metabolism-related genes were assessed by applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic HTR2A and hepatic lipogenic gene expression, and treatment with an HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO mice, and brain 5-HT and HTR2C expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment.
Disease Models & Mechanisms. 2022, 15(7), dmm049612.
新大院博(医)第1105号
Persistent ID (NDL): info:ndljp/pid/12970409
https://dl.ndl.go.jp/pid/12970409
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
https://dl.ndl.go.jp/collections/A00014
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2023-08-04T23:03:36+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): http://hdl.handle.net/10191/0002001052
https://niigata-u.repo.nii.ac.jp/records/2001052
Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション
https://dl.ndl.go.jp