Alcohol-Induced Hepatic Steatosis: A Comparative Study to Identify Possible Indicator(s) of Alcoholic Fatty Liver Disease.

Abstract

Fatty liver is an early sign of both nonalcoholic and alcoholic fatty liver diseases. Ethanol feeding using a Lieber-DeCarli liquid diet (LD) model which contains 35% fat to rats or mice is a well-established model for alcoholic fatty liver. However, LD diet alone can also induce fatty liver and its differential metabolic profile may be able to differentiate steatosis induced by LD versus LD plus ethanol. We investigated the lipidomic differences in the livers of Sprague-Dawley (SD) rats fed a pellet diet (PD), LD and liquid ethanol diet (LED) for six weeks. Male Sprague Dawley rats were fed with nonalcoholic diets PD, LD or LED (ethanol in LD) for six weeks. Lipids were extracted and analyzed by nuclear magnetic resonance (NMR)- based metabolomics. The NMR data obtained was analyzed by multivariate Principal Component Analysis (PCA) and Spotfire DecisionSite 9.0 software to compare PD versus LD and LD versus LED groups. PCA of the NMR spectral data of livers of both comparisons showed a clear separation of PD from LD group and LD from LED group indicating differences in lipid profiles which corresponded with changes in total lipid weights. LD showed increases for cholesterol, esterified cholesterol, cholesterol acetate and triglycerides with decreases for fatty acyl chain, diallylic and allylic protons, while the LED showed increases in esterified cholesterol, cholesterol acetate, fatty acid methyl esters, allylic protons and some triglyceride protons with decreases in free cholesterol and phosphatidylcholine (PC). Our data suggest that altered lipid signature or PC levels could be an indicator to differentiate between nonalcoholic versus alcoholic fatty liver.