PPARα is a key regulator of hepatic FGF21
PPARα is a key regulator of hepatic FGF21
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DOI：
10.1016/j.bbrc.2007.06.068
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发表时间：
2007-08-24
影响因子：
3.1
通讯作者：
Rudling, Mats
中科院分区：
文献类型：
--
作者：
Lundasen, Thomas;Hunt, Mary C.;Rudling, Mats
代谢调节剂成纤维细胞生长因子21（FGF 21）在糖尿病和肥胖症的动物模型中具有抗糖尿病特性。使用定量RT-PCR，我们在这里表明，FGF 21的肝脏基因表达受过氧化物酶体增殖物激活受体α（PPAR α）的调节。禁食或用PPARa激动剂Wy-14，643处理小鼠分别诱导FGF 21 mRNA增加10倍和8倍。相比之下，FGF 21 mRNA在PPARa缺陷小鼠中较低，并且禁食或用Wy-14，643处理不诱导FGF 21。肥胖ob/ob小鼠，已知其具有增加的PPAR α。水平，显示肝FGF 21 mRNA水平增加12倍。通过Wy-14，643诱导人原代肝细胞中的FGF 21 mRNA显示了PPARa对人肝脏中的FGF 21表达的潜在重要性，并且在人和小鼠FGF 21启动子中鉴定了PPARa应答元件。对人类中通过PPAR α调节FGF 21的机制的进一步研究将具有极大的兴趣。(C)2007年爱思唯尔公司All rights reserved.
The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPAR alpha). Fasting or treatment of mice with the PPARa agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARa deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPAR alpha. levels, displayed 12-fold increased hepatic FGF21 rnRNA levels. The potential importance of PPARa for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPAR alpha response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPAR alpha in humans will be of great interest. (C) 2007 Elsevier Inc. All rights reserved.