权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanism for down-regulation of GLUT4 by high-fat diet

高脂饮食下调GLUT4的机制

基本信息

批准号：
12671131
负责人：
EZAKI Osamu
金额：
$ 2.18万
依托单位：
National Institute of Health and Nutrition
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671131/
关键词：
GLUT4 Cis-element Insulin resistance High-fat diet Adipose tissue Transgenic mice

项目摘要

GLUT4, the insulin responsive-glucose transporter, mediates the rate limiting step of glucose metabolism in skeletal muscles and adipose tissues. High-fat feeding downregulates GLUT4 mRNA and decreases in insulin-stimulated glucose uptake in white adipose tissues (WAT). By using 5 -deleted mouse GLUT4 minigene transgenic mice, we have demonstrated that adipocyte specific element (s) of mouse GLUT4 are located within 45 bps between -551 and -506 relative to transcription initiation site, while high fat responsive element (s) is located within 150 bps between -701 and -551.DNase I footprinting analysis revealed that nuclear extract in WAT from both high-carbohydrate and high-fat diet fed mice protected the region from -705 to 682 (correspond to NF-1 site) and from -673 to 651 from DNase I digestion. This result showed that nuclear proteins bind to these regions regardless diet. Transgenic animal study indicated that mutation of NF-1 site near 701 abolished GLUT4 expression specially in white adipose tissues. These data suggest that a putative adipocyte specific enhancer binds both NF-1 and 45 bps between 551 and 506, while high-fat diet responsive enhancer binds 150 bps between 701 and 551 with some interaction to adipocyte specific enhancer.

GLUT 4是胰岛素反应性葡萄糖转运蛋白，介导骨骼肌和脂肪组织中葡萄糖代谢的限速步骤。高脂喂养下调GLUT 4 mRNA，并减少胰岛素刺激的葡萄糖摄取在白色脂肪组织（WAT）。通过使用5 -缺失的小鼠GLUT 4小基因转基因小鼠，我们已经证明小鼠GLUT 4的脂肪细胞特异性元件位于相对于转录起始位点的-551和-506之间的45 bp内，而高脂肪响应元件位于-701和-701之间的150个基点内551.DNase I足迹分析显示，来自高碳水化合物和高脂肪饮食喂养的小鼠的WAT中的核提取物保护-705至682（对应于NF-1位点）和-673至651的区域免受DNase I消化。这一结果表明，无论饮食如何，核蛋白都与这些区域结合。转基因动物研究表明，NF-1基因701位点的突变使GLUT 4基因表达下降，尤其是在白色脂肪组织中。这些数据表明，假定的脂肪细胞特异性增强子结合NF-1和551和506之间的45 bp，而高脂饮食反应性增强子结合701和551之间的150 bp，与脂肪细胞特异性增强子有一些相互作用。