Lundåsen Thomas, Hunt Mary C, Nilsson Lisa-Mari, Sanyal Sabyasachi, Angelin Bo, Alexson Stefan E H, Rudling Mats
Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine, M63, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Biochem Biophys Res Commun. 2007 Aug 24;360(2):437-40. doi: 10.1016/j.bbrc.2007.06.068. Epub 2007 Jun 21.
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 (PPARalpha). Fasting or treatment of mice with the PPARalpha agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARalpha deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARalpha levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARalpha for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARalpha response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARalpha in humans will be of great interest.
代谢调节因子成纤维细胞生长因子21（FGF21）在糖尿病和肥胖症动物模型中具有抗糖尿病特性。通过定量逆转录聚合酶链反应（RT-PCR），我们在此表明FGF21的肝脏基因表达受过氧化物酶体增殖物激活受体α（PPARα）调控。禁食或用PPARα激动剂Wy-14,643处理小鼠分别使FGF21 mRNA诱导增加10倍和8倍。相反，PPARα缺陷小鼠中的FGF21 mRNA水平较低，禁食或用Wy-14,643处理均未诱导FGF21。已知PPARα水平升高的肥胖ob/ob小鼠，其肝脏FGF21 mRNA水平增加了12倍。Wy-14,643诱导人原代肝细胞中FGF21 mRNA，这也表明PPARα对人肝脏中FGF21表达也具有潜在重要性，并且在人和小鼠FGF21启动子中均鉴定出了PPARα反应元件。进一步研究PPARα在人类中调节FGF21的机制将非常有趣。
