葡萄糖、果糖及蔗糖诱导鹅肝脂质沉积的差异与调控机制研究

High intensive overfeeding method of fatty liver production limits the development of fatty liver industry. It has been found that high sugar diet can induce lipid deposition in liver. It is of great significance if the fatty liver cab be produced by adding sugar in feed. Our previous research found that the effect of glucose and fructose on the lipids deposition was significantly different, and it is speculated that the regulatory mechanism of lipid deposition by different type of sugar in the liver is different. In this study, firstly, the effect of sucrose, fructose, and glucose on lipid deposition in cellular level was studied, and the role of fatty acid synthesis, fatty acid oxidation, lipids transport and endoplasmic reticulum stress in the hepatocytic steatosis induced-by sugar is explored. Meanwhile, sucrose, fructose and glucose are added in feed, and geese were given a free choice access to diets or overfeeding. The effect of the different types of sugar on goose fatty liver performance and regulation mechanism of lipids deposition in liver is measured. Finally, the sugar which easier induces liver lipid deposition and is less prone to producing inflammation is screened. The method of adding sugar and reducing overfeeding feed amount is researched. The results can not only understand the mechanism of different sugar types in the induction of fat goose liver formation, and provide theoretical basis for the waterfowl fatty liver production and the prevention and treatment of human fatty liver.

高强度填饲生产肥肝的方法限制了肥肝产业的发展，研究发现高糖饮食能够诱导肝脂质大量沉积，如果能通过添加糖减少填饲量生产肥肝将具有重要意义。课题组前期研究发现葡萄糖和果糖对肝脏脂质沉积的影响明显不同，推测不同类型的糖对肝内脂质沉积的调控机制存在差异。本项目首先通过在细胞水平系统研究葡萄糖、果糖和蔗糖调控鹅肝细胞脂质沉积的差异，探讨脂肪酸合成、脂肪酸氧化、脂质转运及内质网应激途径在糖诱导的肝细胞脂肪变性中的作用机制；然后通过在饲料中添加蔗糖、果糖、葡萄糖对鹅进行自由采食或填饲，研究个体水平不同类型的糖对鹅产肝性能及肝脂质沉积调控机制的差异；最后通过分析筛选容易诱导肝脏脂质沉积而不易产生炎症的糖类，探讨通过在肥肝生产中添加糖减轻填饲量的可行性。该项目结果不仅可以弄清不同类型糖在鹅肥肝形成中的作用机制，同时对指导水禽肥肝生产及人类脂肪肝的防治提供理论依据。

在个体水平通过在饲料添加葡萄糖、果糖和蔗糖生产鹅肥肝，研究不同类型的糖诱导的肥肝生成和鹅肝脏脂质沉积的差异，在细胞水平用葡萄糖、果糖和蔗糖培养鹅肝细胞探讨不同类型的糖诱导鹅肝细胞脂质沉积的分子调控机制。实验结果显示葡萄糖、果糖和蔗糖均能显著增加鹅肝脏内的脂质沉积，显著提高肥肝中不饱和脂肪酸含量，其中果糖和蔗糖的诱导效果较好，鹅肥肝肝品质和脂肪酸含量结果表明，10%果糖每日填饲五次对玉米粉填饲的肥肝重量和肥肝品质的改进具有良好的效果。糖类能够改变脂质合成、脂质氧化、脂质转运相关、脂解作用以及细胞增殖途径相关基因的表达水平，糖类能够增强肠道消化酶活性和肠道消化吸收能力，肠道微生物群 (主要是厚壁菌门) 通过肠-肝轴 (尤其是果糖和蔗糖) 促进了肝脏内脂质生成及沉积。细胞实验结果显示，通过在鹅原代肝细胞中转染FAS、CPT1A和MTP基因的干扰载体或过表达载体能够明显改变肝细胞内脂质沉积，葡萄糖、果糖和蔗糖能够通过脂肪酸合成、脂肪酸氧化及脂质转运三个途径促进肝细胞内脂质沉积，并且FAS、CPT1A和MTP基因的干扰载体或过表达载体与三种糖类共同培养肝细胞显著改变糖类诱导的脂质沉积。内质网应激在加糖填饲诱导的肝脂肪变性中不起作用，但在糖类诱导的肝细胞脂质沉积中起重要调控作用。与葡萄糖相比，果糖和蔗糖能够促进鹅免疫性能的提高，抑制炎症的发生。该结果为通过在填饲饲料中添加糖类生产肥肝降低填饲强度提供依据。