Fig. 3
From: Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease
Mechanisms of ethanol-induced liver injury. Ethanol can upregulate lipid synthase and FA transporter activity to increase lipid synthesis and downregulate lipid transporters and β-oxidases to reduce lipid consumption, which eventually leads to lipid accumulation. ROS produced by ethanol oxidative metabolism triggers the release of proinflammatory cytokines and activates a variety of immune cells to release chemokines and cytokines, leading to immuno-inflammatory responses. Ethanol also inhibits tight junctions to disrupt the intestinal barrier, inducing intestinal LPS translocation to further stimulate the inflammatory response in the liver. In hepatocytes, ROS and lipid peroxidation products generated during ethanol metabolism activate oxidative stress and ER stress reactions in multiple organ systems. ACE and FAEEs, metabolites of ethanol, also induce mitochondrial dysfunction. ROS, reactive oxidative species; LPS lipopolysaccharide; FAs fatty acids; ER stress Endoplasmic reticulum stress; ACE acetaldehyde; FAEEs Fatty acid ethyl esters