Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol

Shengmin Yan, Jun Zhou, Xiaoyun Chen, Zheng Dong, Xiao Ming Yin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Alcoholic 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 Atg7 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 autophagy 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.

Original languageEnglish (US)
Pages (from-to)1744-1762
Number of pages19
JournalAmerican Journal of Pathology
Volume189
Issue number9
DOIs
StatePublished - Sep 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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