• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
【24h】

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation

机译：胆汁酸通过促进细胞内甲状腺激素活化而诱导能量消耗

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

While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways(1,2), are ligands for the G-protein-coupled receptor ( GPCR) TGR5(3,4) and activate nuclear hormone receptors such as farnesoid X receptor alpha ( FXR-alpha; NR1H4)(5-7). FXR-alpha regulates the enterohepatic recycling and biosynthesis of BAs by controlling the expression of genes such as the short heterodimer partner (SHP; NR0B2)(8,9) that inhibits the activity of other nuclear receptors. The FXR-alpha-mediated SHP induction also underlies the downregulation of the hepatic fatty acid and triglyceride biosynthesis and very-low-density lipoprotein production mediated by sterol-regulatory-element-binding protein 1c(10). This indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators. Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2(-/-) mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption. These effects are independent of FXR-alpha, and instead are mediated by increased cAMP production that stems from the binding of BAs with the G-protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism because they coexpress D2 and TGR5. The BA - TGR5 - cAMP - D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control.
机译：尽管人们早已知道胆汁酸（BAs）在膳食脂质吸收和胆固醇分解代谢中必不可少，但近年来，随着信号分子的出现，胆汁酸（BAs）发挥了重要作用。 BAs激活有丝分裂原激活的蛋白激酶途径（1,2），是G蛋白偶联受体（GPCR）TGR5（3,4）的配体，并激活核激素受体，例如法尼醇X受体α（FXR-alpha; NR1H4 ）（5-7）。 FXR-α通过控制诸如抑制其他核受体活性的短异二聚体伴侣（SHP; NR0B2）（8,9）等基因的表达来调节BAs的肠肝循环和生物合成。 FXR-α介导的SHP诱导也是肝脏脂肪酸和甘油三酸酯生物合成的下调和由固醇调节元素结合蛋白1c（10）介导的低密度脂蛋白生产的基础。这表明BAs可能能够作为一般的代谢整合剂而超出BA动态平衡的控制范围。在这里，我们表明对小鼠施用BAs会增加棕色脂肪组织中的能量消耗，从而防止肥胖和胰岛素抵抗。 BAs的这种新的代谢作用严重取决于诱导依赖于环AMP的2型甲状腺素激活素碘甲状腺素脱碘酶（D2），因为它在D2（-/-）小鼠中丢失。 BA处理棕色脂肪细胞和人骨骼肌细胞会增加D2活性和耗氧量。这些作用与FXR-α无关，而是由BAs与G蛋白偶联受体TGR5结合产生的cAMP产量增加介导。在啮齿动物和人类中，最热最重要的组织都通过这种机制专门靶向，因为它们共同表达D2和TGR5。因此，BA-TGR5-cAMP-D2信号传导途径是微调能量稳态的关键机制，可用于改善代谢控制。

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