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

Abstract

Background. Fatty liver is an early sign of both nonalcoholic and alcoholic fatty liver diseases. Ethanol feeding using a LieberDeCarli 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. Purpose. 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. Study design. 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. Results. 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). Conclusion. Our data suggest that altered lipid signature or PC levels could be an indicator to differentiate between nonalcoholic versus alcoholic fatty liver.

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

“…One reason was that the model can effectively emulate the human typical drinking pattern; [ 22 ] the other one was that ethanol‐free Lieber‐DeCarli liquid diet may induce hepatic steatosis because of the relatively high fat content. [ 29 ] Generally, an adult can ingest 100 mg of Lf every day, accounting for 1/500 of total protein consumption. The Lf doses in clinical trials ranged from 200 to 3600 mg day −1 , [ 30–35 ] and mainly concentrated in 1 g day −1 , [ 31–34 ] which is equal to decuple daily dose.…”

Proton NMR Enables the Absolute Quantification of Aqueous Metabolites and Lipid Classes in Unique Mouse Liver Samples

“…In most studies that used proton NMR-based metabolomics for liver samples, analyses have been performed on either aqueous extracts or lipidic extracts. Those analyses employed spectral binning, followed by multivariate statistical analyses to highlight changes in metabolite composition due to disease [11][12][13][14], alcohol consumption [15][16][17], or contaminant exposure [18].…”