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Role of KLF15 on Energy metabolic regulation

KLF15 在能量代谢调节中的作用

基本信息

批准号：
18590988
负责人：
SAKAUE Hiroshi
金额：
$ 2.43万
依托单位：
Kinki University (2007)Kobe University (2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

1. KLF15 expression during the development of obesityWe have shown that the expression of the KLF15 gene is markedly down-regulated during the development of obesity in ob/ob mice and high fat-diet mice.2. Construction of adipocyte-specific KLF15 transgenic miceWe have made the 'adipocyte-specific KLF15 transgenic mice under the aP2-promoter. The amounts of KLF15 were increased by an 〜1-fold or 〜3-fold increase in white adipose tissue in line 1 or line 3 transgenic mice, respectively3. Metabolic analysis in adipocyte-specific KLF15 transgenic mice fed a normal chaw diet. The mass of white adipose tissue did not differ significantly between wild-type mice and KLF15 transgenic mice fed a normal chaw diet. However, the plasma concentration of adiponectin decreased in KLF15 transgenic mice.4. Metabolic analysis in adipocyte-specific KLF15 transgenic mice fed a high fat dietThe high fat diet increased the adipocyte mass in wild-type mice. In contrast, maintain of adipocyte-specific KLF15 transgenic mice on the high fat diet did not increase body weight and adipocyte mass. Moreover, an oral glucose tolerance test revealed marked glucose tolerance in adipocyte-specific KLF15 transgenic mice.5. Metabolic analysis in adipocyte-specific KIF15 transgenic ob/ob miceWe generated ob/ob mice with adipocyte-specific overexpression of KLF15. ob/ob mice with adipocyte-specific overexpression of KLF15 were found to smaller the their ob/ob litermates. This difference in body weight was attributable at least in part to smaller white adipose tissue in the former animals.6. Role of KLF15 on SCD1 expressionFeeding with the high fat diet resulted in a marked up-regulation of the amount of SCD1 in white adipose tissue. This up-regulation of SCD1 during the development of obesity was not observed in adipocyte-specific KLF15 transgenic mice. In conclusion, KLF15 regulates adipocyte hypertrophy via the expression of SCD1/

1.KLF15基因在肥胖小鼠和高脂饮食小鼠肥胖形成过程中的表达我们发现，KLF15基因在肥胖小鼠和高脂饮食小鼠肥胖形成过程中的表达明显下调。脂肪细胞特异性KLF15转基因小鼠的构建我们在aP2启动子作用下获得了脂肪细胞特异性KLF15转基因小鼠。转基因小鼠的白色脂肪组织中KLF15的含量分别增加了~1倍和~3倍。饮食正常的脂肪细胞特异性KLF15转基因小鼠的代谢分析。野生型小鼠和KLF15转基因小鼠的白色脂肪组织质量没有显著差异。而KLF15转基因小鼠血浆脂联素浓度降低。高脂饮食对脂肪细胞特异性KLF15转基因小鼠代谢的影响高脂饮食增加了野生型小鼠的脂肪细胞质量。相比之下，脂肪细胞特异性KLF15转基因小鼠在高脂饮食中的维持不会增加体重和脂肪细胞质量。此外，口服葡萄糖耐量试验显示，脂肪细胞特异性KLF15转基因小鼠具有明显的葡萄糖耐量。脂肪细胞特异性KIF15转基因ob/ob小鼠的代谢分析我们建立了脂肪细胞特异性高表达KLF15的ob/ob小鼠。脂肪细胞特异性过表达KLF15的Ob/ob小鼠被发现比他们的ob/ob文盲伴侣更小。体重的差异至少部分归因于前一组动物较小的白色脂肪组织。KLF15在SCD1表达中的作用喂饲高脂饲料后，白色脂肪组织中SCD1量明显上调。在脂肪细胞特异的KLF15转基因小鼠中，没有观察到在肥胖发展过程中SCD1的这种上调。综上所述，KLF15通过SCD 1/2的表达调控脂肪细胞肥大