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AKR1A1 deficiency is associated with high risk of alcohol‐induced fatty liver syndrome
Author(s) -
Chen WanRu,
Lan YingWei,
Chen HsiaoLing,
Chen ChuanMu
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.546.6
Subject(s) - cyp2e1 , steatohepatitis , steatosis , alcohol dehydrogenase , chemistry , medicine , endocrinology , alcoholic liver disease , ethanol metabolism , aldehyde dehydrogenase , glutathione , liver injury , superoxide dismutase , oxidative stress , glutathione reductase , aspartate transaminase , fatty liver , biochemistry , cirrhosis , ethanol , biology , glutathione peroxidase , alkaline phosphatase , enzyme , cytochrome p450 , disease
Alcoholic liver disease(ALD) is caused by excessive alcohol consumption. The spectrum of alcohol‐related liver injury varies from hepatic steatosis, steatohepatitis, alcoholic fibrosis to irreversible cirrhosis. AKR1A1 is a member of the aldo‐keto reductase (AKR) superfamily, which catalyze the reduction of various aldehydes to their corresponding alcohols in an NADPH‐dependent manner. The enzyme is encoded by the AKR1A1 gene that protects cells against oxidative stress and detoxification. The aim of this study is to identify the role of AKR1A1 deficiency in mouse hepatic diseases after chronic alcohol exposure. In this study, we have established a novel strain of AKR1A1 knockout (KO) mice, which integrated the pCAG‐eGFP transgene and simultaneously deleted 17kb of the AKR1A1 gene locus. The AKR1A1 KO mice ( AKR1A1 eGFP/eGFP ) reduced ascorbic acid biosynthesis, may affect aldehyde reductase metabolism. Male AKR1A1 eGFP/eGFP and CD‐1 control mice were divided into four groups(n=6) that fed either the Lieber‐Decarli diet containing 5 % ethanol (Ethanol‐fed) or an isocaloric (Pair‐fed) control diet for 8 weeks. In comparison with ethanol exposure‐CD‐1 control mice, the ethanol exposure‐ AKR1A1 eGFP/eGFP mice showed a significant increase in the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels (p<0.05), and the levels of pro‐inflammatory cytokines (TNF‐α and IL‐1β), hepatic triglycerides(TG) and cytochrome P4502E1(CYP2E1) were also elevated. However, the levels of antioxidant enzymes, including hepatic glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) were significantly reduced in the ethanol exposure‐ AKR1A1 KO mice. The histological analysis observed that ethanol exposure‐ AKR1A1 eGFP/eGFP mice developed fatty liver syndrome, but not observed in the ethanol exposure‐CD‐1 control mice. In conclusion, we demonstrated that chronic exposure of alcohol lead to lack of hepatic steatosis and inflammation in AKR1A1 KO mice, which may provide a novel insight into the role of AKR1A1 in alcoholic liver disease. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .