Lipid droplet-associated proteins in alcoholic liver disease: a potential linkage with hepatocellular damage

Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the physiological settings. In addition, recent lipidology studies have revealed that expression of the lipid droplet-associated proteins possibly participate in the pathologic processes of many metabolic disorders, including fatty liver and insulin resistance. Hence, controlling protein expressions is expected to offer novel therapeutic options. In this review, we summarize collected data concerning the potential contribution of the lipid droplet-associated proteins to the development of alcoholic fatty liver. Without exception, existing data indicates that the lipid droplet-associated proteins, especially the perilipin family proteins, are important factors in alcoholic fatty liver. These proteins exert a prosteatotic effect, and their expression is closely associated with lipotoxicity based on endoplasmic reticulum stress and oxidative injury. Although suppression of their expression may be beneficial, careful consideration is required because these proteins simultaneously function as protective factors against lipotoxicity.