Analysis of hepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet
Analysis of hepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet
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DOI：
10.1507/endocrj.ej12-0258
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发表时间：
2013-03-01
影响因子：
2
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
--
作者：
Nojima, Koji;Sugimoto, Ken;Rakugi, Hiromi
遗传因素和致糖尿病的环境因素，如高糖饮食（HSD），都参与了2型糖尿病的发展。在这项研究中，Nagoya-Shibata-Yasuda（NSY）小鼠，2型糖尿病的动物模型和C3 H小鼠作为对照，从断奶开始喂食HSD、高脂饮食（HFD）或常规饮食（RD）。在C3 H小鼠中，BED显著增加体重增加，但维持葡萄糖耐量。相反，在NSY小鼠中，HSD导致体重增加和肝脏脂肪变性增加，葡萄糖耐受不良增加的程度大于HFD。此外，我们进行了DNA微阵列分析，以检测HSD下两种菌株的肝脏基因表达水平的差异。然后，我们对选定的基因进行RT-PCR分析，以评估RD条件下的基础表达水平和HSD条件下的变化。饲喂HSD的NSY小鼠（而非C3 H小鼠）表现出Pparg 2（Pparg的同种型）以及G 0 s2（Pparg的靶点）的肝脏表达水平增加，已知这两种基因是脂肪细胞特异性基因。与RD喂养的C3 H小鼠相比，Kat 2b（转录调节），Hsd 3b 5（类固醇激素代谢）和Cyp 7 b1（胆汁酸代谢）的肝脏表达水平最初在RD喂养的NSY小鼠中较低，并在HSD-fed NSY小鼠中进一步降低。与C3 H小鼠相比，无论饮食条件如何，NSY小鼠中金属硫蛋白（Mt 1）和金属硫蛋白2（Mt 2）的表达均显著降低。这些数据表明，阐明这种异质性响应HSD可能有助于进一步了解导致人类糖尿病的基因-环境相互作用。
Both genetic factors and diabetogenic environmental factors, such as a high-sucrose diet (HSD), are involved in the development of type 2 diabetes. In this study, the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of type 2 diabetes and C3H mice used as controls, were fed a HSD, a high-fat diet (HFD) or a regular diet (RD) from weaning. In C3H mice, BED significantly increased body weight gain, but maintained glucose tolerance. In contrast, in NSY mice, HSD resulted in increased body weight gain and liver steatosis and increased glucose intolerance to a greater extent than HFD. Furthermore, we performed DNA microarray analysis to detect differences in hepatic gene expression levels in both strains under HSD. We then performed RT-PCR analysis on selected genes to evaluate basal expression level under RD and changes under HSD conditions. HSD-fed NSY, but not C3H mice, exhibited increased hepatic expression levels of Pparg2, an isoform of Pparg as well as G0s2, a target of Pparg, which are known to be adipocyte-specific genes. Compared to RD-fed C3H mice, hepatic expression levels of Kat2b (transcriptional regulation), Hsd3b5 (steroid hormone metabolism) and Cyp7b1 (bile acid metabolism) were initially lower in RD-fed NSY mice, and were further decreased in HSD-fed NSY mice. Expression of Metallothionein (Mt1) and Metallothionein 2 (Mt2) was significantly lower in NSY mice compared to C3H mice, irrespective of dietary condition. These data suggest that elucidation of this heterogeneity in response to HSD might contribute to further understanding of the gene-environment interactions leading to diabetes in humans.