A Western diet with alcohol in drinking water recapitulates features of alcohol-associated liver disease in mice.
A Western diet with alcohol in drinking water recapitulates features of alcohol-associated liver disease in mice.
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DOI：
10.1111/acer.14700
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发表时间：
2021-10
期刊：
影响因子：
--
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中科院分区：
文献类型：
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酒精相关肝病的小鼠模型在实施的难易程度和产生的病理学方面差异很大。这包括 Lieber-DeCarli 液体饮食中的脂肪变性和轻度炎症，以及 Tsukamoto-French 胃内喂养模型中看到的严重炎症、纤维化和焦亡。所有这些模型的实施都受到协议的劳动密集型性质和成功胃内喂养所需的专业技能的限制。因此，我们寻求开发一种新模型，以最小的操作要求重现酒精引起的炎症和纤维化的特征。小鼠随意喂食颗粒状高脂肪西方饮食（40％的热量来自脂肪），并在饮用水中添加酒精。我们发现，当酒精浓度每周 4 天在 20% 与 3 天在 10% 之间交替变化时，就会达到最佳饮酒量。对照小鼠接受仅加水的西方饮食颗粒，总喂养时间为 16 周。男性饮酒量为 18-20 克/公斤/天，女性为 20-22 克/公斤/天。饮酒组中的雄性小鼠和雌性小鼠在 12 周和 10 周后血清 ALT 和 AST 均升高。第 16 周时，雄性和雌性均出现肝脏炎症、脂肪变性和细胞周纤维化。食用不含酒精的西方饮食的对照小鼠仅出现轻度脂肪变性。喂食酒精的小鼠表现出 HNF4α 的 mRNA 和蛋白表达降低，HNF4α 是肝细胞分化的主要调节因子，其下调是酒精性肝炎肝细胞衰竭的已知驱动因素。一个易于管理的 16 周西方饮食酒精模型概括了人类酒精相关脂肪性肝炎的炎症、纤维化和基因表达方面。
Mouse models of alcohol-associated liver disease vary greatly in their ease of implementation and the pathology they produce. This ranges from steatosis and mild inflammation in Lieber-DeCarli liquid diet, and severe inflammation, fibrosis and pyroptosis seen in the Tsukamoto-French intragastric feeding model. Implementation of all these models is limited by the labor-intensive nature of the protocols and the specialized skills necessary for successful intragastric feeding. We thus sought to develop a new model that would reproduce features of alcohol-induced inflammation and fibrosis with minimal operational requirements. Mice were fed ad libitum with a pelleted high fat western diet (40% calories from fat) and alcohol added to the drinking water. We found that optimal alcohol consumption occurred when alcohol concentration alternated between 20% for 4 days and 10% for 3 days per week. Control mice received western diet pellets with water alone and the total feeding duration was 16 weeks. Alcohol consumption was 18–20 g/kg/day in males and 20–22 g/kg/day in females. Mice in the alcohol groups developed elevated serum ALT and AST after 12 weeks in males and 10 weeks in females. At 16 weeks, both males and females developed liver inflammation, steatosis and pericellular fibrosis. Control mice on western diet without alcohol had mild steatosis only. Alcohol fed mice showed reduced mRNA and protein expression of HNF4α, the master regulator of hepatocyte differentiation, downregulation of which is a known driver of hepatocellular failure in alcoholic hepatitis. A simple to administer, 16-week western diet alcohol model recapitulates the inflammatory, fibrotic and gene expression aspects of human alcohol-associated steatohepatitis.
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DOI：
10.1016/j.alcohol.2020.03.007
发表时间：
2020-08
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Coker CR;Aguilar EA;Snyder AE;Bingaman SS;Graziane NM;Browning KN;Arnold AC;Silberman Y
通讯作者：
Silberman Y
DOI：
10.1111/j.1530-0277.2011.01472.x
发表时间：
2011-07-01
影响因子：
3.2
作者：
Gaebele, Erwin;Dostert, Karin;Hellerbrand, Claus
通讯作者：
Hellerbrand, Claus
影响因子：
3.1
作者：
Gelineau RR;Arruda NL;Hicks JA;Monteiro De Pina I;Hatzidis A;Seggio JA
通讯作者：
Seggio JA
DOI：
10.1007/s005340070034
发表时间：
2000-01-01
期刊：
Journal of hepato-biliary-pancreatic surgery
影响因子：
--
作者：
Kono, H;Bradford, B U;Thurman, R G
通讯作者：
Thurman, R G
影响因子：
2.8
作者：
Crabbe, John C.;Harkness, John H.;Metten, Pamela
通讯作者：
Metten, Pamela