|Wang, Yan - Tufts University|
|Seitz, Helmut - University Of Heidelberg|
|Wang, Xiang-dong - Tufts University|
Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2009
Publication Date: 3/1/2010
Citation: Wang, Y., Seitz, H., Wang, X. 2010. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats. Alcoholism: Clinical and Experimental. 34(3):567-573.
Interpretive Summary: Liver inflammation, caused by a high fat diet and obesity is called “Nonalcoholic steatohepatitis.” It has been recognized as a severe stage of nonalcoholic fatty liver disease. This is the most common form of chronic liver disease in the United States. However, it is not clear if people with an inflamed liver (Nonalcoholic steatohepatitis) who drink alcohol will have a greater amount of liver inflammation and damage. In the present study, we show that alcohol consumption even at a moderate level (1~2 drinks/day) by a person with non-alcoholic steatohepatitis condition led to more liver inflammation and cell death. Our results suggest that people with an inflamed liver should take great caution when consuming alcohol. Our results may also help to explain why certain patients with an inflamed liver have a higher risk of advanced liver diseases, such as liver cancer.
Technical Abstract: 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-a (TNFa) and TNF receptor 1 (TNFR1), 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 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 two groups than those in the control group. Conclusions: This data suggests that even moderate alcohol consumption can cause more hepatic inflammation and cellular apoptosis in a pre-existing NASH condition.