386 Dietary Saturated and Unsaturated Fat Differentially Modulate Gut Microbiome, Intestinal Barrier and Liver Injury in a Mouse Model of Alcoholic Liver Disease

barrier dysfunction and hepatic endoplasmic reticulum (ER) stress and injury, which are recognized etiologic factors in ALD. We examined hepatic and intestinal effects of acrolein and alcohol using in vitro (rat hepatic H4IIEC, and human intestinal epithelial Caco2 cells) and in vivo (C57/Bl6 mice chronic+binge alcohol feeding) models. ACR adducts accumulated in response to alcohol or ACR in mouse livers and intestines, and in cultured cells. This was accompanied by hepatic steatosis, activation of JNK, ER stress (upregulation of ATF3, ATF4, and pro-apoptotic CHOP), mitochondrial disruption and apoptosis as seen by Cellomics. Notably, the cytotoxic effects of ACR and alcohol were attenuated by acrolein/ aldehyde scavengers. Alcohol-induced in vivo intestinal effects (down-regulation of tight junction proteins ZO-1, occludin, and claudin, and barrier dysfunction) were mimicked by ACR in Caco2 cells. Our study demonstrates that acrolein is an important mediator of the hepatic and intestinal effects of alcohol consumption, and suggests a therapeutic potential for acrolein scavengers in ALD.