Selenoneine Ameliorates Hepatocellular Injury and Hepatic Steatosis in a Mouse Model of NAFLD
Selenoneine Ameliorates Hepatocellular Injury and Hepatic Steatosis in a Mouse Model of NAFLD
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DOI：
10.3390/nu12061898
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发表时间：
2020-06-01
期刊：
影响因子：
5.9
通讯作者：
Yamashita, Michiaki
中科院分区：
文献类型：
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作者：
Miyata, Masaaki;Matsushita, Koki;Yamashita, Michiaki
硒氨酸是一种新型有机硒化合物，在鱼类的血液、肌肉和其他组织中显著存在。本研究旨在确定硒氨酸是否能减轻非酒精性脂肪性肝病（NAFLD）小鼠模型中的肝细胞损伤和肝脂肪变性。缺乏法脂样X受体（FXR）的小鼠被用作脂肪肝疾病的模型，因为它们表现出肝肿大、肝脂肪变性和肝脏炎症。fxr阴性小鼠连续4个月饲喂含硒0.3 mg /kg的饲粮。用富含硒氨酸的饮食喂养inFxr-null小鼠，发现肝肿大、肝损伤相关诊断标志物、肝甘油三酯和总胆汁酸水平显著降低。硒氨酸组肝脏和血凝块总硒浓度分别是对照组的1.7倍和1.9倍。硒氨酸组的肝脏和血凝块中发现了明显的硒氨酸积累。硒氨酸组氧化应激相关基因（血红素加氧酶1（Hmox1）、谷胱甘肽s-转移酶α 1（Gsta1）和gsta2）、脂肪酸合成基因（硬脂酰辅酶a去饱和酶1（Scd1）和乙酰辅酶a羧化酶1(Acc1)）和硒蛋白（谷胱甘肽过氧化物酶1（Gpx1）和硒蛋白P(Selenop)）的表达量显著降低。这些结果表明硒氨酸可以减轻NAFLD小鼠模型中的肝脂肪变性和肝细胞损伤。
Selenoneine is a novel organic selenium compound markedly found in the blood, muscles, and other tissues of fish. This study aimed to determine whether selenoneine attenuates hepatocellular injury and hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice lacking farnesoid X receptor (FXR) were used as a model for fatty liver disease, because they exhibited hepatomegaly, hepatic steatosis, and hepatic inflammation.Fxr-null mice were fed a 0.3 mg Se/kg selenoneine-containing diet for four months. Significant decreases in the levels of hepatomegaly, hepatic damage-associated diagnostic markers, hepatic triglycerides, and total bile acids were found inFxr-null mice fed with a selenoneine-rich diet. Hepatic and blood clot total selenium concentrations were 1.7 and 1.9 times higher in the selenoneine group than in the control group. A marked accumulation of selenoneine was found in the liver and blood clot of the selenoneine group. The expression levels of oxidative stress-related genes (heme oxygenase 1(Hmox1),glutathione S-transferase alpha 1(Gsta1), andGsta2), fatty acid synthetic genes (stearoyl CoA desaturase 1(Scd1) andacetyl-CoA carboxylase 1(Acc1)), and selenoprotein (glutathione peroxidase 1(Gpx1) andselenoprotein P(Selenop)) were significantly decreased in the selenoneine group. These results suggest that selenoneine attenuates hepatic steatosis and hepatocellular injury in an NAFLD mouse model.