FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
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DOI：
10.1016/j.celrep.2015.10.021
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Kieffer, Timothy J.
中科院分区：
文献类型：
--
作者：
Kwon, Michelle M.;O'Dwyer, Shannon M.;Kieffer, Timothy J.
成纤维细胞生长因子21 （FGF21）介导的体重减轻和葡萄糖代谢的改善与脂肪组织中解偶联蛋白1 （Ucp1）水平的增加相关，表明Ucp1依赖性的生热作用可能驱动FGF21的作用。据报道，在没有UCP1的情况下，FGF21在减轻体重和改善葡萄糖稳态方面同样有效。我们发现，尽管FGF21可以降低野生型和Ucp1敲除小鼠的体重，但在缺乏Ucp1的情况下，FGF21对葡萄糖的快速清除存在缺陷。此外，在肥胖野生型小鼠中，葡萄糖漂移期间棕色脂肪组织（BAT）温度下降，FGF21改善葡萄糖清除，同时阻止BAT温度下降。在Ucp1基因敲除小鼠中，葡萄糖漂移期间BAT温度的下降和fgf21介导的BAT温度变化都消失了。我们得出结论，fgf21介导的葡萄糖挑战清除的改善需要UCP1，并唤起UCP1依赖的产热作用作为增加葡萄糖处理的方法。
Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.