高果糖、高脂饲料喂养小鼠肝脏脂质合成酶类与内质网应激相关因子蛋白表达变化

目的 探讨和比较高果糖、高脂饮食诱导的小鼠肝脏三酰甘油(TG)的发生机制及其与内质网应激的关系.方法 成年雄性C57BL/J6小鼠45只,质量25～30 g,按随机数字表随机均分为对照组、高脂组及高果糖组,每组15只.对照组予以普通饲料,高果糖组予以高糖饮食,高脂组予以高脂饮食,3组每日进食热量基本相等,经喂养8周后对小鼠行葡萄糖耐量(ipGTT)实验,处死小鼠后测定各组肝脏三酰甘油含量,并测定肝脏脂质合成酶类和内质网应激相关因子的蛋白表达.结果 不同饲料喂养8周后,高果糖组和高脂组的附睾脂肪含量均为(2.0±0.1)g/100 g(质量),明显高于对照组(1.2±0.1)g/100 g(质量)P＜0.01].高果糖组和高脂组ipGTT实验后的血糖曲线下面积明显高于对照组(P＜0.01).与对照组相比,高果糖组和高脂组的肝脏TG水平显著增高(P＜0.01),其中高果糖组肝脏TG升高更明显,高果糖组肝脏TG水平显著高于高脂组(P＜0.01).与对照组相比,高果糖组的乙酰辅酶A羧化酶( ACC)、脂肪酸合成酶(FAS)、硬脂酰辅酶A去饱和酶(SCD-1)表达增加(P＜0.01),而高脂组的FAS、ACC、SCD-1的表达减少(P＜0.05)；反应内质网应激的磷酸化胰腺内质网激酶(p-PERK)、山梨醇要求激酶-1(p-IRE-1/t-IRE-1)和葡萄糖调节蛋白78(GRP78)蛋白表达在高果糖组和高脂组均增加(P值均＜0.01).结论 高果糖饮食和高脂饮食均可引起脂肪肝,二者通过不同机制引起脂肪肝,高果糖饮食促进内源性脂质生成,高脂喂养抑制肝内源性脂质生成,两种饮食均可诱发内质网应激,提示内质网应激与饮食因子诱导的脂肪肝的发生发展有关.

The variation of lipogenic enzymes and endoplasmic reticulum stress markers expression in high-fat or high-fructose fed mice

Objective To explore and compare the mechanism of high-fructose and high-fat diet induced triglyceride excessive accumulation in mice liver and its relationship with endoplasmic reticulum (ER) stress.Methods 45 Adult male C57BL/J6 mice,weight arranged from 25 gram to 30 gram were randomly divided into control group,high-fructose group and high-fat group,15 mice in each group.Common food was fed in control group,high-fructose food was fed in high-fructose group,high-fat food was fed in high-fat group,and the everyday calories consumption in 3 groups was almost equal.Intraperitoneal glucose tolerance test (ipGTT) was performed after feeding for 8 weeks.After mice were sacrificed,triglyceride content,lipogenic enzymes and ER stress markers expression in liver tissues of each group were measured.Results After feeding with different food for 8 weeks,the fat content of epididymis in high-fructose group and high-fat group both was (2.0±0.1) g/100 g (body weight),which was significantly higher than that of control group (1.2 ± 0.1) g/100 g (body weight),P＜0.01).After ipGTT test,the area under curve of blood glucose in high-fructose group and high-fat group was significantly higher than that in control group (P＜0.01).Compared with control group,triglyceride contents of liver tissues in high-fructose group and high-fat group were significantly increased,of those triglyceride contents in high-fructose group increased more obviously,and triglyceride contents in high-fructose group was significantly higher than that of high-fat group (P＜0.01).Compared with control group,the expression of acylCoA carboxylase (ACC),fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1) increased in high-fructose group (P＜0.01),while decreased in high-fat group (P＜0.05) ; meanwhile,the expression of phosphorylated pancreatic ER kinase (p-PERK),inositol requiring enzyme 1 (p-IRE-1/t-IRE-1)and glucose-regulated protein 78 (GRP78) was up-regulated in both high-fructose group and high-fat group (all P＜0.01).Conclusion Both high-fructose diet and high-fat diet can induce fatty liver through different mechanisms.High-frucose diet promotes endogenous lipogenesis while high-fat diet inhibits endogenous lipogenesis.Both dietary factors can induce ER stress,which indicate that ER stress is associated with pathogenesis and development of food factors induced fatty liver.