New insights in the pathogenesis of alcohol-related liver disease:The metabolic,immunologic,and neurologic pathways  

作　　者：Tom Ryu Kyurae Kim Sung Eun Choi Katherine Po Sin Chung Won-Il Jeong 

机构地区：[1]Laboratory of Liver Research,Graduate School of Medical Science and Engineering,KAIST,Daejeon,Republic of Korea

出　　处：《Liver Research》2023年第1期1-8,共8页肝脏研究（英文）

基　　金：supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT,Korean goverment(2021R1A2C3004589,2014M3A9D5A01073556).

摘　　要：Alcohol-related liver disease(ALD)became an important health issue worldwide.Following chronic alcohol consumption,the development of ALD might be caused by metabolic and immunologic factors,such as reactive oxygen species(ROS)and pro-inflammatory cytokines.For example,hepatic cytochrome P4502E1 enzyme increases ROS production and stimulates de novo lipogenesis after alcohol exposure.In addition,damage-and pathogen-associated molecular patterns stimulate their specific receptors in nonparenchymal cells,including Kupffer cells,hepatic stellate cells(HSCs),and lymphocytes,which result in hepatocyte death and infiltration of pro-inflammatory cells(e.g.,neutrophils and macrophages)in the liver.Moreover,our studies have suggested the novel involvement of neurologic signaling pathways(e.g.,endocannabinoid and glutamate)through the metabolic synapse between hepatocytes and HSCs in the development of alcohol-related hepatic steatosis.Additionally,agouti-related protein and beta2-adrenergic receptors aggravate hepatic steatosis.Furthermore,organ-crosstalk has emerged as a critical issue in ALD.Chronic alcohol consumption induces dysbiosis and barrier disruption in the gut,leading to endotoxin leakage into the portal circulation,or lipolysis-mediated transport of triglycerides from the adipose tissue to the liver.In summary,this review addresses multiple pathogeneses of ALD,provides novel neurologic signaling pathways,and emphasizes the importance of organ-crosstalk in the development of ALD.

关 键 词：Alcohol-related liver disease(ALD) Cannabinoid receptor STEATOHEPATITIS Lipopolysaccharide(LPS) Metabotropic glutamate receptor(mGluR) Toll-like receptor 4(TLR4) 

分 类 号：R575[医药卫生—消化系统]