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成纤维细胞生长因子21抑制脂肪细胞瘦素基因表达的分子机制

陈镝, 赵妍妍, 梁向艳, 张丽君, 魏兰兰, 谢荣, 张小春, 苏兴利, 赵玉峰^*

西安医学院基础医学部基础医学研究所，西安 710021

摘要

本研究旨在明确成纤维细胞生长因子21 (fibroblast growth factor 21, FGF21)调控脂肪细胞瘦素基因表达的分子机制。 以3T3-F442A脂肪细胞为研究对象，用荧光定量RT-PCR检测瘦素mRNA表达，并用Western blot检测信号转导通路蛋白的磷 酸化水平。结果显示，FGF21显著下调脂肪细胞瘦素mRNA表达水平，FGF21受体抑制剂BGJ-398完全阻断此作用。FGF21 上调脂肪细胞ERK1/2和AMPK的磷酸化水平，ERK1/2抑制剂SCH772984和AMPK抑制剂Compound C分别可部分阻断FGF21 抑制瘦素基因表达的作用，二者联合应用可完全阻断FGF21的抑制作用。PI3K抑制剂LY294002和Akt抑制剂AZD5363对 FGF21抑制瘦素基因表达的作用无明显影响。以上结果提示，FGF21可能通过FGF受体激活脂肪细胞ERK1/2和AMPK两条信 号途径，抑制瘦素基因表达。

关键词： 成纤维细胞生长因子21; 瘦素; 胞外信号激活蛋白激酶1/2; AMP激活蛋白激酶; 脂肪细胞

分类号：R335.9

The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes

CHEN Di, ZHAO Yan-Yan, LIANG Xiang-Yan, ZHANG Li-Jun, WEI Lan-Lan, XIE Rong, ZHANG Xiao-Chun, SU Xing-Li, ZHAO Yu-Feng^*

Institute of Basic Medical Sciences, Department of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, China

Abstract

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.

Key words: fibroblast growth factor 21; leptin; ERK1/2; AMPK; adipocytes

收稿日期：2019-09-06　　录用日期：2020-01-20

通讯作者：赵玉峰　　E-mail: yufeng.zhao@xiyi.edu.cn

DOI: 10.13294/j.aps.2020.0022

引用本文：

陈镝, 赵妍妍, 梁向艳, 张丽君, 魏兰兰, 谢荣, 张小春, 苏兴利, 赵玉峰. 成纤维细胞生长因子21抑制脂肪细胞瘦素基因表达的分子机制[J]. 生理学报 2020; 72 (2): 175-180.

CHEN Di, ZHAO Yan-Yan, LIANG Xiang-Yan, ZHANG Li-Jun, WEI Lan-Lan, XIE Rong, ZHANG Xiao-Chun, SU Xing-Li, ZHAO Yu-Feng. The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes. Acta Physiol Sin 2020; 72 (2): 175-180 (in Chinese with English abstract).