鹅肥肝形成过程中内质网应激作用的研究

项目名称： 鹅肥肝形成过程中内质网应激作用的研究

项目编号： No.31472086

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 畜牧学与草地科学

项目作者： 耿拓宇

作者单位： 扬州大学

项目金额： 88万元

中文摘要： 鹅肥肝味美、有营养且生产工艺独特。揭示其形成机制将有助于解决肥肝生产面临的问题。研究表明哺乳动物的肝细胞内质网应激对胰岛素抵抗的形成十分重要，而胰岛素抵抗可诱发高胰岛素血症，促进脂肪合成。由于鹅在脂肪代谢方面的特点，该机制是否适用于鹅脂肪肝/肥肝尚不清楚。本研究将利用荧光定量PCR和免疫印迹法在鹅原代肝细胞和活体水平测定高能营养因子是否激活内质网应激信号通路，诱导下游标识基因的过表达，抑制AKT的磷酸化，引起胰岛素抵抗。利用干扰RNA抑制标识基因的过表达，可确定内质网应激与胰岛素抵抗间的因果关系。还将使用药物或调节饲料成分，确定调节内质网应激是否引起鹅出现胰岛素抵抗（高血糖、高胰岛素血症等），并促进肥肝形成。为加深对内质网应激作用的理解以及寻找相关候选基因为分子育种奠定基础，本研究将筛选内质网应激的靶基因。总之，本研究旨在阐明内质网应激对鹅肥肝形成的作用。

中文关键词： 鹅；脂肪肝；内质网应激；胰岛素抵抗；分子机制

英文摘要： Goose fatty liver is delicious, nutritious, and expensive, and the technique for its production is unique. The industry of fatty liver faces some problems including forced feeding, uneven quality, high cost, and breeding difficulty. Revealing the mechanisms underlying the development of fatty liver may help address these problems. A few mechanisms were identified in some model mammals, but it is unknown these mechanisms are applicable to goose fatty liver due to the differences in lipid metabolism between goose and mammals. Recent studies indicate in mammals endoplasmic reticulum stress (ERS) plays an important role in the occurrence of hepatic insulin resistance (IR). Insulin resistance may induce hyperinsulinemia, which in turn promotes lipogenesis. In this study, quantitative PCR and immunoblotting will be used to determine whether treating both goose primary hepatocytes and geese with energy-rich nutrients activates the signaling pathways of ERS, induces overexpression of CHOP and TRIB3, the marker genes of ERS, and results in suppression of AKT phosphorylation and thus IR. This will be followed by assays with interfering RNA to determine the relationship between ERS and IR. It will also be determined whether the regulation of ERS by chemicals or adjustment of dietary components induces IR and hyperinsulinemia and promotes the development of fatty liver. To deepen the understanding of the role of ERS, target genes regulated by ERS will be identified. These genes may be used in future selection and breeding as fatty liver associated candidate genes. In summary, this study is aimed to addressing the role of ERS in the development of goose fatty liver.

英文关键词： goose;fatty liver;endoplasmic reticulum stress;insulin resistance;molecular mechanism