Leptin as a Potential Regulator of FGF21
Leptin as a Potential Regulator of FGF21
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DOI：
10.1159/000443070
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Jornayvaz, Francois R.
中科院分区：
文献类型：
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作者：
Asrih, Mohamed;Veyrat-Durebex, Christelle;Jornayvaz, Francois R.
背景/目标：成纤维细胞生长因子21（FGF 21）是一种有效的代谢调节剂，已被证明可以改善胰岛素抵抗动物模型的胰岛素敏感性。一些研究集中在确定FGF 21效应的介质。然而，参与FGF 21调节的因素的鉴定还远未完成。由于瘦素也是一种有效的代谢调节剂，我们的目的是表征瘦素是否可以调节FGF 21。研究方法：我们研究了瘦素在Wistar大鼠体内和体外使用人源性肝癌HepG 2细胞对FGF 21的潜在调节。选择该模型是因为肝脏被认为是主要的FGF 21表达位点。结果：我们发现，瘦素注射增加成年Wistar大鼠血浆FGF 21水平。这在体外得到证实，因为瘦素增加了HepG 2细胞中的FGF 21表达。我们还发现，瘦素对FGF 21表达的影响是通过激活HepG 2细胞中的STAT 3介导的。结论：本研究提供了有关瘦素-STAT 3-FGF 21轴的新发现，尽管仍需要研究瘦素和FGF 21之间的确切机制。这些结果在确定治疗与胰岛素抵抗相关的代谢疾病（如肥胖和2型糖尿病）的潜在新临床方法方面具有极大的意义。(C)2016作者（s）由S. Karger AG，巴塞尔
Background/Aims: Fibroblast growth factor 21 (FGF21), a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes. (C) 2016 The Author(s) Published by S. Karger AG, Basel