Hepatic gene expression and lipid parameters in complement C3−/− mice that do not develop ethanol-induced steatosis

Background/AimsFatty infiltration initiates alcohol-induced liver changes and complement component C3 affects lipid metabolism. We recently observed that ethanol-induced steatosis seen in normal (C3+/+) mice was absent in livers of C3-deficient (C3−/−) mice. To understand the underlying molecular mechanisms we analyzed lipid parameters and liver gene expression profiles in these mice.MethodsA Western-type high-fat diet with ethanol or carbohydrates (control) was fed for 6 weeks to C3+/+ and C3−/− mice. Serum and liver lipid parameters were analyzed and liver mRNA expression patterns studied by micro-array analysis and RT-PCR.ResultsIn both genotypes ethanol markedly reduced serum cholesterol, apolipoprotein A-I, phospholipid transfer protein activity and hepatic mRNA levels of fatty acid-binding proteins and fatty acid β-oxidation enzymes. In contrast, exclusively in C3−/− mice, ethanol treatment increased serum and liver adiponectin levels but down-regulated transcripts of lipogenic enzymes, adiponectin receptor 2 and adipose differentiation-related protein and up-regulated phospholipase D1.ConclusionsWe propose that these ethanol-induced alterations observed exclusively in C3−/− mice contribute to protection against fatty infiltration and subsequent inflammatory processes in the liver of these mice. The results suggest important cross-talk between complement factor C3 and lipid regulators in ethanol-induced steatosis.