Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats.
BACKGROUND
Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition.


METHODS
Sprague-Dawley rats were first fed ad libitum with Lieber-DeCarli high-fat diet (71% energy from fat) for 6 weeks to induce NASH, as demonstrated previously. Afterwards, these rats were continuously fed with high-fat diet (HFD, 55% total energy from fat) or high fat plus alcohol diet (HFA, 55% energy from fat and 16% energy from alcohol) for an additional 4 weeks. Pathological lesions including fat accumulation and inflammatory foci in liver were examined and graded. Lipid peroxidation and apoptotic hepatocytes in the liver were assessed. The mRNA expressions of tumor necrosis factor-alpha (TNFalpha) and TNF receptor 1 (TNF-R1), Fas death receptor (Fas) and Fas ligant (FasL), IL-1beta and IL-12 were determined by real-time PCR. Protein levels of total and cleaved caspase-3, CYP2E1, Bax, and Bcl-2 were measured by western blotting.


RESULTS
The number of hepatic inflammatory foci and apoptotic hepatocytes were significantly increased in rats fed with HFA as compared with those in HFD-fed rats. The aggravated inflammatory response and cellular apoptosis mediated by HFA were associated with elevated mRNA expression of Fas/FasL and cleaved caspase-3 protein. Although no significant differences were observed between HFD and HFA groups, the levels of lipid peroxidation, Bax and Bcl-2 protein concentration, and mRNA levels of other inflammatory cytokines were significantly higher in these 2 groups than those in the control group.


CONCLUSIONS
These data suggest that even moderate alcohol consumption can cause more hepatic inflammation and cellular apoptosis in a pre-existing NASH condition.
Wang
Yan
Y
Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Seitz
Helmut K
HK
Wang
Xiang-Dong
XD
D000428:Alcohol Drinking / Q000009:adverse effects* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D004041:Dietary Fats; D000431:Ethanol