Yan, ShengminZhou, JunChen, XiaoyunDong, ZhengYin, Xiao-Ming2019-08-152019-08-152019Yan, S., Zhou, J., Chen, X., Dong, Z., & Yin, X.-M. (2019). Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol. The American Journal of Pathology. https://doi.org/10.1016/j.ajpath.2019.05.011https://hdl.handle.net/1805/20404Alcoholic fatty liver disease is often complicated by other pathologic insults, such as viral infection or high-fat diet. Autophagy plays a homeostatic role in the liver but can be compromised by alcohol, high-fat diet, or viral infection, which in turn affects the disease process caused by these etiologies. To understand the full impact of autophagy modulation on alcohol-induced liver injury, several genetic models of autophagy deficiency, which have different levels of functional alterations, were examined after acute binge or chronic-plus-binge treatment. Mice given alcohol with either mode and induced with deficiency in liver-specific autophagy-related protein (Atg)-7 shortly after the induction of Atg7 deletion had elevated liver injury, indicating the protective role of autophagy. Constitutive hepatic Atg7–deficient mice, in which Atg7 was deleted in embryos, were more susceptible with chronic-plus-binge but not with acute alcohol treatment. Constitutive hepatic Atg5–deficient mice, in which Atg5 was deleted in embryos, were more susceptible with acute alcohol treatment, but liver injury was unexpectedly improved with the chronic-plus-binge regimen. A prolonged Atg deficiency may complicate the hepatic response to alcohol treatment, likely in part due to endogenous liver injury. The complexity of the relationship between autophagy deficiency and alcohol-induced liver injury can thus be affected by the timing of autophagy dysfunction, the exact autophagy gene being affected, and the alcohol treatment regimen.enPublisher Policyliver injuryalcoholautophagyArticle