Repin1 deficiency in liver tissue alleviates NAFLD progression in mice
Repin1 deficiency in liver tissue alleviates NAFLD progression in mice
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DOI：
10.1016/j.jare.2018.11.003
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发表时间：
2019-03-01
影响因子：
10.7
通讯作者：
Vollmar, Brigitte
中科院分区：
文献类型：
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作者：
Abshagen, Kerstin;Mense, Lars;Vollmar, Brigitte
肥胖和代谢综合征的发病率越来越高，这促进了非酒精性脂肪性肝病(NAFLD)的发展，这种疾病可以演变为肝硬变和肝细胞癌。Repin1的缺失以前被证明对脂肪和葡萄糖代谢以及肥胖调节有有益的影响。在这里，我们描述了肝脏Repin1(LRep1-/-)缺失的小鼠的NAFLD。为此，用链脲佐菌素/高脂饮食或对照饮食治疗的雄性LRep1/-和野生型小鼠的肝病被分析了20周。链脲佐菌素/高脂饮食处理的LRep1-/-小鼠的全身和肝脏脂肪堆积显著减少，伴随着慢性炎症减轻，随后肝脏损伤减轻。值得注意的是，Repin1基因缺陷的小鼠表现出较低的肿瘤患病率和肿瘤频率，以及降低了肝脏重量/体重指数。在NAFLD的早期阶段使用Repin1 siRNA的治疗方法证实了Repin1缺乏症的观察到的有益效果。这项研究提供的证据表明，肝脏中Repin1的缺失可以减缓NAFLD的进展，这很可能是通过减少脂肪堆积和减轻慢性组织炎症来实现的。因此，调控Repin1的表达可能成为抑制NAFLD进展的新策略和潜在工具。(C)2018年作者。由Elsevier B.V.代表开罗大学出版。
There is an increasing prevalence of obesity and metabolic syndrome, which promote the development of non-alcoholic fatty liver disease (NAFLD), a disease that can evolve into cirrhosis and hepatocellular carcinoma. Repin1 loss was previously shown to have beneficial effects on lipid and glucose metabolism and obesity regulation. Herein, we characterized NAFLD in mice with hepatic deletion of Repin1 (LRep1 -/-). For this purpose, liver disease was analysed in male LRep1 -/- and wild-type mice treated with streptozotocin/high fat diet or a control diet over a period of 20 wks. Streptozotocin/high fat diet treated LRep1 -/- mice showed a significant decrease in systemic and hepatic lipid accumulation, accompanied by diminished chronic inflammation and a subsequent reduction in liver injury. Remarkably, Repin1-deficient mice exhibited a lower tumour prevalence and tumour frequency, as well as a reduced liver weight/body weight index. A therapeutic approach using Repin1 siRNAin the early phase of NAFLD verified the observed beneficial effects of Repin1 deficiency. This study provides evidence that loss of Repin1 in the liver attenuates NAFLD progression, most likely by reducing fat accumulation and alleviating chronic tissue inflammation. Thus, modulating Repin1 expression may become a novel strategy and potential tool to inhibit NAFLD progression. (C) 2018 The Authors. Published by Elsevier B.V. on behalf of Cairo University.