Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.