Up-Regulation of Stearoyl-CoA Desaturase 1 Increases Liver MUFA Content in Obese Zucker but Not Goto-Kakizaki Rats

Up-Regulation of Stearoyl-CoA Desaturase 1 Increases Liver MUFA Content in Obese Zucker but Not Goto-Kakizaki Rats
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DOI:
10.1007/s11745-013-3786-2
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发表时间:
2013-05-01
期刊:
影响因子:
1.9
通讯作者:
Kudo, Naomi
Kudo, Naomi
中科院分区:
医学4区
文献类型:
--
作者:
Karahashi, Minako;Ishii, Fumiko;Kudo, Naomi

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Goto-Kakizaki(GK)大鼠是自发性非肥胖2型糖尿病的动物模型。尽管有大量的证据表明代谢紊乱,但关于GK大鼠肝脏脂肪酸代谢的信息很少。本研究旨在探讨GK大鼠肝脏脂肪酸谱的特征,特别是MUFA,以及脂肪酸谱改变的机制。将参与MUFA生物合成的酶的活性、编码这些酶的基因的表达以及肝脏中的脂肪酸谱与肥胖Zucker(fa/fa)(ZF)大鼠(肥胖且非糖尿病)的那些进行比较。硬脂酰辅酶A去饱和酶(SCD)的活性和SCD 1基因的表达显着上调GK大鼠,这些水平在很大程度上与ZF大鼠。然而,与ZF大鼠相比,考虑到GK大鼠肝脏中SCD活性的高度升高,油酸和棕榈油酸的比例和含量非常低。ZF大鼠的棕榈酰辅酶A链延长(PCE)活性和脂肪酸延长酶(Elov 16)基因表达显著上调,而GK大鼠的PCE活性上调幅度较小,Elov 16基因表达无变化。这些结果表明Elov 16沿着SCD 1的基因表达的上调对于提高肝脏中油酸的比例和含量是必不可少的。
The Goto-Kakizaki (GK) rat is an animal model for spontaneous-onset, non-obese type 2 diabetes. Despite abundant evidence about disorders in metabolism, little information is available about fatty acid metabolism in the liver of GK rats. This study aimed to investigate the characteristics of the fatty acid profile, particularly MUFA, and the mechanism underlying the alterations in fatty acid profiles in the liver of GK rats. The activities of enzymes that participate in the biosynthesis of MUFA, expressions of genes encoding these enzymes, and the fatty acid profile in the liver were compared with those of obese Zucker (fa/fa) (ZF) rats, which are obese and non-diabetic. Stearoyl-CoA desaturase (SCD) activity and SCD1 gene expression were considerably up-regulated in GK rats, and these levels were largely comparable to those in ZF rats. However, the proportions and contents of oleic acid and palmitoleic acid were very low considering the highly elevated activity of SCD in the liver of GK rats, when compared with ZF rats. Palmitoyl-CoA chain elongation (PCE) activity and fatty acid elongase (Elovl6) gene expression were markedly up-regulated in ZF rats, whereas PCE activity was up-regulated much less and Elovl6 gene expression was unchanged in GK rats. These results suggest the possibility that up-regulation of gene expression of Elovl6 along with SCD1 is indispensable to elevate the proportions and contents of oleic acid in the liver.