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跨膜4超家族成员5（TM4SF5）介导的异常摄食行为和阿片肽表达促进非酒精性脂肪性肝病特征。

TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features.

作者信息

Pinanga Yangie Dwi, Lee Han Ah, Shin Eun-Ae, Lee Haesong, Pyo Kyung-Hee, Kim Ji Eon, Lee Eun Hae, Kim Wonsik, Kim Soyeon, Kim Hwi Young, Lee Jung Weon

机构信息

Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

Department of Internal Medicine, Ewha Womans University College of Medicine, Division of Gastroenterology and Hepatology, Ewha Womans University Mokdong Hospital, Seoul 07985, Republic of Korea.

出版信息

iScience. 2023 Aug 14;26(9):107625. doi: 10.1016/j.isci.2023.107625. eCollection 2023 Sep 15.

DOI:10.1016/j.isci.2023.107625
PMID:37670786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10475478/
Abstract

Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered mice fed normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and knockout mice, hepatocyte-specific TM4SF5-overexpressing -TG (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal β-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal β-oxidation, mTOR, and autophagy.

摘要

跨膜4L六家族成员5（TM4SF5）参与非酒精性脂肪性肝炎（NASH），但其作用机制尚不清楚。对采用正常食物或高脂饮食喂养一整天或采用日间喂养（DF）模式的基因工程小鼠进行代谢参数分析。与野生型和敲除小鼠相比，肝细胞特异性过表达TM4SF5的转基因（TG）小鼠在小鼠非活动的白天表现出异常的食物摄入行为、阿片肽表达增加、食物摄入量增加以及更高水平的NASH特征。对TG小鼠进行DF或外源性阿片肽注射会导致严重的肝脏病变。TM4SF5介导的异常食物摄入与过氧化物酶体β氧化、mTOR激活和自噬抑制相关，并引发NASH表型。非酒精性脂肪性肝病（NAFLD）患者的样本显示血清阿片肽与NAFLD活动评分之间存在相关性。总之，这些观察结果表明，肝脏中的TM4SF5可能通过调节过氧化物酶体β氧化、mTOR和自噬来导致异常的食物摄入行为，从而引发脂肪性肝炎特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/363dac4315a0/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/ee4a870f3632/gr2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/68bdf69eeeeb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/4e412651b911/gr5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/5c3eb39db810/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/363dac4315a0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/e93539928374/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/33ea2ed6c37f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/ee4a870f3632/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/7d9a8bc49a85/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/68bdf69eeeeb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/4e412651b911/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/da29297d8a8c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/5c3eb39db810/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/10475478/363dac4315a0/gr8.jpg

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