短期高果糖喂养对小鼠肝脏脂质沉积和胰岛素敏感性的影响

Effect of short-term high-fructose feeding on liver triglyceride content and hepatic insulin sensitivity in mice

目的:探讨短期高果糖饮食对小鼠肝脏甘油三酯含量及胰岛素敏感性的影响。方法:雄性C57BL/J6小鼠分为对照组及高果糖组,经喂养3 d后对小鼠行腹腔葡萄糖耐量试验,处死小鼠后测定各组肝脏甘油三酯含量,采用HE染色观察肝脏组织的病理改变;测定肝脏脂质合成酶类的蛋白表达,同时通过比较各组注射与未注射胰岛素的小鼠磷酸化Akt/总Akt(p-Akt/t-Akt)和磷酸化GSK-3α/β/总GSK-3α/β(p-GSK-3α/β/t-GSK-3α/β)表达变化评估肝脏胰岛素敏感性。结果:喂养3 d后,与对照组相比,高果糖组葡萄糖耐量曲线下面积和肝腔甘油三酯均显著增加(均P<0.01),同时肝组织HE染色显示高果糖组小鼠肝细胞已有明显脂滴沉积;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)和硬脂酰辅酶A脱饱和酶-1(SCD-1)表达显著增加(均P<0.01);胰岛素注射后,与对照组相比,高果糖组的p-Akt/t-Akt及p-GSK-3α/β/t-GSK-3α/β均显著降低(均P<0.01)。结论:3 d高果糖饮食即可引起肝脏脂质沉积,脂质沉积与果糖刺激FAS、ACC和SCD-1表达增加有关;肝脏脂质沉积的同时伴有肝脏胰岛素抵抗发生。

AIM： To investigate the effect of short-term high-fructose feeding on liver triglyceride content and hepatic insulin sensitivity in mice.METHODS： Male C57BL/J6 mice were divided into control group and high（HFru） fructose group.After 3-day feeding,intraperitoneal glucose tolerance test（ipGTT） was performed to evaluate whole-body insulin sensitivity.The mice were sacrificed,and the liver samples were collected for measuring the liver triglyceride content and observing the pathological changes of the liver under light microscope with HE staining.The protein levels of lipogenic enzymes in the liver tissues were measured.To evaluate the hepatic insulin sensitivity,the protein levels（expressed as the ratio） of phosphorylated Akt/total Akt（p-Akt/t-Akt） and phosphorylated GSK-3α/β/total GSK-3α/β（p-GSK-3α/β/t-GSK-3α/β） were compared between 2 groups of the mice with or without insulin injection.RESULTS： After 3-day feeding of high-fructose diet,compared with control group,the area under the curve of ipGTT and triglyceride contents in the liver tissues were significantly increased in HFru group.HE staining of the liver in the mice in HFru group showed obvious lipid droplet formation.Compared with control group,the protein expression of acetyl-CoA carboxylase（ACC）,fatty acid synthase（FAS） and stearoyl-CoA desaturase 1（SCD-1） was significantly increased in HFru group.After insulin injection,the ratio of p-Akt/t-Akt and p-GSK-3α/β/t-GSK-3α/β was significantly decreased in HFru group as compared with control group.CONCLUSION： A 3-day short-term high-fructose feeding induces liver steatosis,which is related to the increased protein expression of FAS,ACC and SCD-1.Liver steatosis occurs simultaneously with the development of hepatic insulin resistance.