The role of insulin and glucose in goose primary hepatocyte triglyceride accumulation
The role of insulin and glucose in goose primary hepatocyte triglyceride accumulation
复制标题
DOI：
10.1242/jeb.022210
复制
发表时间：
2009-05-15
影响因子：
2.8
通讯作者：
Pan, Zhixiong
中科院分区：
文献类型：
--
作者：
Han, Chunchun;Wang, Jiwen;Pan, Zhixiong
为了了解鹅脂肪肝的发生机制，我们研究了胰岛素和葡萄糖在鹅原代肝细胞甘油三酯(TG)蓄积中的作用。分离鹅原代肝细胞，用胰岛素和葡萄糖处理。与对照组相比，100和150nmoll(-1)胰岛素组大鼠的TG蓄积、乙酰辅酶A羧基酶α(ACCα)和脂肪酸合成酶(Fas)活性以及固醇调节元件结合蛋白-1(SREBP-1)、Fas和ACCα基因的mRNA水平均升高。200nmoll(-1)的胰岛素抑制TG的积累和ACC、Fas的活性，但上调SREBP-1、Fas和ACCα的基因表达。我们还发现，高糖(30mmoll(-1))增加了甘油三酯水平、ACC和Fas活性，以及SREBP-1和Fas的mRNA水平。但高糖对ACCA基因表达水平无明显影响。此外，胰岛素与葡萄糖的相互作用可诱导Tg蓄积、ACC和Fas活性以及SREBP-1、Fas和ACCα基因的表达，并增加SREBP-1核蛋白水平和核SREBP-1与ACC基因SRE反应元件的结合。结果还表明，当肝细胞与30mmoll(-1)葡萄糖共同培养96h后，葡萄糖诱导的甘油三酯积聚减少。综上所述，胰岛素和葡萄糖可能通过调节鹅肝细胞中造脂基因的表达和造脂酶的活性来影响肝脏的造脂作用，SREBP-1可能在造脂基因的协同激活中起重要作用。我们认为利用肝细胞内蓄积的甘油三酯是鹅肝细胞脂肪变性可逆现象的原因。
In order to obtain some information on how fatty liver arises in geese, we investigated the role of insulin and glucose in triglyceride (TG) accumulation in goose primary hepatocytes. Goose primary hepatocytes were isolated and treated with insulin and glucose. Compared with the control group, 100 and 150nmoll(-1) insulin increased TG accumulation, acetyl-CoA carboxylase-alpha (ACC alpha) and fatty acid synthase (FAS) activity, and the mRNA levels of sterol regulatory element-binding protein-1 (SREBP-1), FAS and ACC alpha genes. Insulin at 200nmoll(-1) had an inhibiting effect on TG accumulation and the activity of ACC and FAS, but increased the gene expression of SREBP-1, FAS and ACC alpha. We also found that high glucose (30mmoll(-1)) increased the TG level, ACC and FAS activity, and the mRNA levels of SREBP-1 and FAS. However, there was no effect of high glucose on ACCa mRNA level. In addition, the interaction between insulin and glucose was observed to induce TG accumulation, ACC and FAS activity, and gene expression of SREBP-1, FAS and ACC alpha, and increase SREBP-1 nuclear protein level and binding of nuclear SREBP-1 and the SRE response element of the ACC gene. The result also indicated that the glucose-induced TG accumulation decreased after 96 h when the hepatocytes were cultured with 30mmoll(-1) glucose. In conclusion, insulin and glucose may affect hepatic lipogenesis by regulating lipogenic gene expression and lipogenic enzyme activity in goose hepatocytes, and SREBP-1 might play an important role in the synergetic activation of lipogenic genes. We propose that the utilization of accumulated TG in hepatocytes is the reason for the reversible phenomenon in goose hepatocellular steatosis.