BACKGROUND & AIMS: Alcoholic steatohepatitis (ASH) is the progressive form of 
alcoholic liver disease and may lead to cirrhosis and hepatocellular carcinoma. 
We studied mouse models and human tissues to identify molecules associated with 
ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human 
cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in 
white adipose tissues and promotes formation of fat droplets.
METHODS: C57BL/6N mice or mice with hepatocyte-specific disruption of Fsp27 
(Fsp27(Hep-/-) mice) were fed the Lieber-Decarli ethanol liquid diet (5% 
ethanol) for 10 days to 12 weeks, followed by 1 or multiple binges of ethanol (5 
or 6 g/kg) during the chronic feeding. Some mice were given an inhibitor 
(GW9662) of peroxisome proliferator-activated receptor γ (PPARG). Adenoviral 
vectors were used to express transgenes or small hairpin (sh) RNAs in cultured 
hepatocytes and in mice. Liver tissue samples were collected from ethanol-fed 
mice or from 31 patients with alcoholic hepatitis (AH) with biopsy-proved ASH 
and analyzed histologically and immunohistochemically and by transcriptome, 
immunoblotting, and real-time PCR analyses.
RESULTS: Chronic-plus-binge ethanol feeding of mice, which mimics the drinking 
pattern of patients with AH, produced severe ASH and mild fibrosis. Microarray 
analyses revealed similar alterations in expression of many hepatic genes in 
ethanol-fed mice and humans with ASH, including up-regulation of mouse Fsp27 
(also called Cidec) and human CIDEC. Fsp27(Hep-/-) mice and mice given 
injections of adenovirus-Fsp27shRNA had markedly reduced ASH following 
chronic-plus-binge ethanol feeding. Inhibition of PPARG and cyclic 
AMP-responsive element binding protein H (CREBH) prevented the increases in 
Fsp27α and FSP27β mRNAs, respectively, and reduced liver injury in this 
chronic-plus-binge ethanol feeding model. Overexpression of FSP27 and ethanol 
exposure had synergistic effects in inducing production of mitochondrial 
reactive oxygen species and damage to hepatocytes in mice. Hepatic CIDEC mRNA 
expression was increased in patients with AH and correlated with the degree of 
hepatic steatosis and disease severity including mortality.
CONCLUSIONS: In mice, chronic-plus-binge ethanol feeding induces ASH that mimics 
some histological and molecular features observed in patients with AH. Hepatic 
expression of FSP27/CIDEC is highly up-regulated in mice following 
chronic-plus-binge ethanol feeding and in patients with AH; this up-regulation 
contributes to alcohol-induced liver damage.