Fat-specific protein 27/CIDEC promotes alcoholic steatohepatitis in mice and humans


Dr. Ming-Jiang Xu

Medical Research Institute at Wuhan University


About the Speaker:

Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland;                                                


Email: mingjiangxu@gmail.com  



Alcoholic steatohepatitis (ASH) is the progressive form of alcoholic liver disease that leads to cirrhosis and hepatocellular carcinoma. There is an urgent need to identify molecular drivers in order to develop targeted therapies. Here the functions of mouse fat-specific protein 27 (Fsp27)/human cell death activator CIDEC (the human homologue of Fsp27) were investigated.


We developed a mouse model with chronic (8 weeks)-plus-binge ethanol feeding, which mimics the drinking patterns of alcoholic hepatitis (AH) patients, produced severe ASH and mild fibrosis. Microarray analyses revealed that mouse Fsp27/human CIDEC gene was increased in this animal model and human ASH samples. Fsp27 is expressed at high levels in adipose tissues but at very low levels in normal liver. Chronic-plus-binge ethanol feeding markedly upregulated hepatic Fsp27 mRNA and protein expression. Silencing the Fsp27 gene by shRNA or genetic disruption ameliorated chronic-plus-binge ethanol-induced ASH. Inhibition of peroxisome proliferator-activated receptor g (PPARg) or cyclic-AMP-responsive-element binding protein H (CREBH) attenuated chronic-plus-binge ethanol-induced elevation of Fsp27a and FSP27b mRNA, respectively, and subsequently ameliorated liver injury. Overexpression of Fsp27 and ethanol exposure synergistically induced mitochondrial reactive oxygen species production and hepatocyte injury in vivo and in vitro, which is likely owing to the mitochondrial location of FSP27 leading to the decreased mitochondrial complex I activity. Finally, hepatic expression of CIDEC mRNA was elevated and positively correlated with hepatic steatosis, disease severity, and mortality in AH patients.


FSP27/CIDEC gene product promotes ASH in chronic-plus-binge ethanol-fed mice and in human AH. Targeting CIDEC gene is likely to be a novel therapeutic targets for the treatment of ASH.


Seminar Time: 2015-12-29


Seminar Room: 医学部行政楼三楼国际会议厅

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