Amelioration of non-alcoholic fatty liver disease with NPC1L1-targeted IgY or n-3 polyunsaturated fatty acids in mice
Amelioration of non-alcoholic fatty liver disease with NPC1L1-targeted IgY or n-3 polyunsaturated fatty acids in mice
复制标题
DOI：
10.1016/j.metabol.2016.10.002
复制
发表时间：
2017-01-01
影响因子：
9.8
通讯作者：
Hahm, Ki-Baik
中科院分区：
文献类型：
--
作者：
Bae, Jin-Sik;Park, Jong-Min;Hahm, Ki-Baik
非酒精性脂肪性肝病（NAFLD）患者进展为肝细胞癌的风险增加，此外还有心血管和严重代谢疾病等合并症;然而，目前的治疗选择有限。基于我们先前的报道，ω-3多不饱和脂肪酸（n-3 PUFAs）可以显著改善高脂饮食（HFD）诱导的NAFLD，我们探索了n-3 PUFAs和N-IgY（一种对尼曼-匹克C1样1（NPC 1 L1）胆固醇转运蛋白具有特异性的鸡蛋黄来源的IgY）对小鼠NAFLD的治疗效果。我们产生了N-IgY，并证实了其在HepG 2和Caco-2细胞中有效的胆固醇转运阻断活性，这与依折麦布（EZM）的作用相当。将能够产生n-3 PUFA的C57 BL/6野生型和fat-1转基因小鼠单独饲喂高脂饮食（HFD）或补充有N-IgY。内源性合成的n-3 PUFAs联合N-IgY可显著降低肝脂肪变性、纤维化和炎症（p
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice. We generated N-IgY and confirmed its efficient cholesterol transport-blocking activity in HepG2 and Caco-2 cells, which was comparable to the effect of ezetimibe (EZM). C57BL/6 wild type and fat-1 transgenic mice, capable of producing n-3 PUFAs, were fed a high fat diet (HFD) alone or supplemented with N-IgY. Endogenously synthesized n-3 PUFAs combined with N-IgY led to significant decreases in hepatic steatosis, fibrosis, and inflammation (p