The Hepatic Lipidome: A Gateway to Understanding the Pathogenes is of Alcohol-Induced Fatty Liver

Chronic alcohol consumption can lead to the development of alcoholic fatty liver disease. The underlying pathogenic mechanisms however, have not been fully elucidated. Here, we review the current state of the art regarding the application of lipidomics to study alcohol’s effect on hepatic lipids. It is clear that alcohol has a profound effect on the hepatic lipidome, with documented changes in the major lipid categories (i.e. fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids and prenol lipids). Alcohol’s most striking effect is the marked change in the hepatic fatty acyl pool. This effect includes increased levels of 18-carbon fatty acyl chains incorporated into multiple lipid species, as well as a general shift toward increased unsaturation of fatty acyl moieties. In addition to our literature review, we also make several recommendations to consider when designing lipidomic studies into alcohol’s effects. These recommendations include integration of lipidomic data with other measures of lipid metabolism, inclusion of multiple experimental time points, and presentation of quantitative data. We believe rigorous analysis of the hepatic lipidome can yield new insight into the pathogenesis of alcohol-induced fatty liver. While the existing literature has been largely descriptive, the field is poised to apply lipidomics to yield a new level of understanding on alcohol’s effects on hepatic lipid metabolism. Keywords: Alcohol, fatty acyls, fatty liver, glycerolipids, glycerophospholipids, lipidomics, prenol lipids, sphingolipids, sterol lipids.