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

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 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.

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  • Authors+Show Affiliations

    ,

    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

    ,

    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Minimal Invasive Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

    ,

    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

    ,

    Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China; Department of Cell Biology and Anatomy, Medical College of Georgia and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia.

    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China. Electronic address: xmyin@iu.edu.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31199920

    Citation

    Yan, Shengmin, et al. "Diverse Consequences in Liver Injury in Mice With Different Autophagy Functional Status Treated With Alcohol." The American Journal of Pathology, 2019.
    Yan S, Zhou J, Chen X, et al. Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol. Am J Pathol. 2019.
    Yan, 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, doi:10.1016/j.ajpath.2019.05.011.
    Yan S, et al. Diverse Consequences in Liver Injury in Mice With Different Autophagy Functional Status Treated With Alcohol. Am J Pathol. 2019 Jun 11; PubMed PMID: 31199920.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol. AU - Yan,Shengmin, AU - Zhou,Jun, AU - Chen,Xiaoyun, AU - Dong,Zheng, AU - Yin,Xiao-Ming, Y1 - 2019/06/11/ PY - 2019/02/01/received PY - 2019/05/01/revised PY - 2019/05/07/accepted PY - 2019/6/15/pubmed PY - 2019/6/15/medline PY - 2019/6/15/entrez JF - The American journal of pathology JO - Am. J. Pathol. N2 - 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 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. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/31199920/Diverse_Consequences_in_Liver_Injury_in_Mice_with_Different_Autophagy_Functional_Status_Treated_with_Alcohol L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(19)30094-X DB - PRIME DP - Unbound Medicine ER -