• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Circulating free fatty acids are increased independently of PPARgamma activity after administration of poloxamer 407 to mice.
【24h】

Circulating free fatty acids are increased independently of PPARgamma activity after administration of poloxamer 407 to mice.

机译：给小鼠施用泊洛沙姆407后，循环中的游离脂肪酸增加而与PPARγ活性无关。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Poloxamer 407 (P-407) is a copolymer surfactant that induces a dose-controlled dyslipidemia in both mice and rats. Human macrophages cultured with P-407 exhibit a concentration-dependent reduction in cholesterol efflux to apolipoprotein A1 (apoA1) linked to downregulation of the ATP-binding cassette transporter A1 (ABCA1). Activators of peroxisome proliferator-activated receptor gamma (PPARgamma), as well as PPARalpha, increase expression of liver X receptor alpha (LXRalpha) in macrophages and promote the expression of ABCA1, which, in turn, mediates cholesterol efflux to apoA1. The present study investigated whether P-407 interferes with this signaling pathway. A transactivation assay was used to evaluate whether P-407 can either activate or inhibit the transcriptional activity of PPARgamma. Because thiazolidinedione drugs (PPARgamma agonists) improve glycemic control in type 2 diabetes by reducing blood glucose concentrations, P-407 was also evaluated for its potential to alter plasma insulin and blood glucose concentrations in wild-type (C57BL/6) and PPARgamma-deficient mice. Additionally, because thiazolidinediones attenuate release of free fatty acids (FFAs) from adipocytes and, consequently, decrease circulating plasma levels of FFAs, plasma concentrations of circulating FFAs were also determined in P-407-treated mice. P-407 was unable to modulate PPARgamma activity in cell-based transactivation assays. Furthermore, P-407 did not perturb plasma insulin and blood glucose concentrations after administration to mice. However, by an as yet unidentified mechanism, P-407 caused a significant increase in the serum concentration of FFAs in mice beginning 3 h after administration and lasting more than 24 h postdosing. It is concluded that P-407 does not interfere with the functional activity of PPARgamma after administration to mice.
机译：泊洛沙姆407（P-407）是一种共聚物表面活性剂，可在小鼠和大鼠中诱发剂量控制的血脂异常。用P-407培养的人巨噬细胞对胆固醇的载脂蛋白A1（apoA1）的胆固醇流出呈浓度依赖性降低，这与ATP结合盒转运蛋白A1（ABCA1）的下调有关。过氧化物酶体增殖物激活受体γ（PPARgamma）和PPARalpha的激活剂可增加巨噬细胞中肝X受体α（LXRalpha）的表达并促进ABCA1的表达，ABCA1进而介导胆固醇向apoA1的流出。本研究调查了P-407是否干扰此信号通路。反激活试验用于评估P-407是否可以激活或抑制PPARgamma的转录活性。由于噻唑烷二酮类药物（PPARgamma激动剂）通过降低血糖浓度来改善2型糖尿病的血糖控制，因此还评估了P-407在改变野生型（C57BL / 6）和PPARgamma缺乏症时血浆胰岛素和血糖浓度的潜力。老鼠。另外，由于噻唑烷二酮减弱了脂肪细胞中游离脂肪酸（FFA）的释放并因此降低了FFA的循环血浆水平，因此在P-407治疗的小鼠中还测定了循环FFA的血浆浓度。在基于细胞的反式激活分析中，P-407无法调节PPARγ的活性。此外，P-407在给小鼠服用后不会干扰血浆胰岛素和血糖浓度。然而，由于尚未确定的机制，P-407引起小鼠FFA血清浓度的显着增加，开始于给药后3小时，给药后持续24小时以上。结论是，在给小鼠施用后，P-407不干扰PPARγ的功能活性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号