Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats

The detrimental effects of chronic and excessive alcohol consumption, e.g., prolonged alcohol intake in excess of approximately 100 g/day, on human health have been well documented (Bloss, 2005; Dawson et al., 2005; Ellison et al., 2001; Hoek and Pastorino, 2002; Seitz and Stickel, 2007; Wang, 2005). Recently, a growing number of evidence shows that “moderate” alcohol consumption without heavy drinking episodes is associated with multiple health benefits and lower risks for some chronic diseases (Koppes et al., 2005; Rimm et al., 1991; Stampfer et al., 2005). The term “moderate alcohol” has been established as 1~2 drinks/day for men (Dawson, 2003), which is equivalent to 14–28 g/day based on the energy value of pure ethanol (Meister et al., 2000). Data from the Framingham Heart Study revealed that the age-adjusted mean alcohol consumption was 21.0~30.6 g/day among adult men and 10.4~14.2 g/day among adult women (Zhang et al., 2008). The inferior limit for the moderate alcohol consumption category is established on 4 drinks/day (Dawson et al., 1995), which accounts for 19.6% of a total 2000 kcal intake. Nonalcoholic steatohepatitis (NASH) has been recognized as a severe stage of nonalcoholic fatty liver disease, the most common form of chronic liver disease in the United States (Ong and Younossi, 2007). Diagnosis of NASH is defined by the concurrence of fat accumulation and infiltration of inflammatory cells in the liver, in the absence of chronic & excessive alcohol consumption history (Brunt, 2005). Certain risk factors for NASH development have been suggested to potentiate the capacity of alcohol-mediated liver damage (Diehl, 2004). Although patients with NASH have been advised against drinking alcohol, experimental evidence is lacking regarding whether alcohol consumption, especially at moderate levels, can increase their susceptibility to more liver injuries. Previously, a high-fat diet induced NASH rat model was developed by feeding rats a 71% liquid high-fat diet enriched with corn oil for three weeks (Lieber et al., 2004). Recently, we demonstrated that a higher rate of cellular apoptosis was induced in this rat model, which was associated with increased hepatic inflammation and oxidative stress (Wang et al., 2008). Since excessive alcohol feeding to rats increased apoptosis (Baroni et al., 1994; Mi et al., 2000; Slomiany et al., 1999), we investigated whether moderate alcohol consumption (16% of total calories intake) with the pre-existing NASH condition, aggravates apoptosis and hepatic inflammation in rats.