Endoplasmic reticulum stress induces up-regulation of hepatic β-Klotho expression through ATF4 signaling pathway

被引：26

作者：

Dong, Kun ^{[1
]}

Li, Huating ^{[1
]}

Zhang, Mingliang ^{[1
]}

Jiang, Shan ^{[1
]}

Chen, Shuqin ^{[1
]}

Zhou, Jian ^{[2
]}

Dai, Zhi ^{[2
]}

Fang, Qichen ^{[1
]}

Jia, Weiping ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Key Lab Diabet Mellitus, Dept Endocrinol & Metab,Shanghai Diabet Inst,Shan, Shanghai 200233, Peoples R China

[2] Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Dept Liver Surg, Shanghai 200032, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 459卷 / 02期

关键词：

Endoplasmic reticulum stress; beta-Klotho; Fibroblast growth factor 21; Non-alcoholic fatty liver disease; GROWTH-FACTOR; 21; FATTY LIVER-DISEASE; METABOLIC-ACTIVITY; PPAR-ALPHA; FGF21; FIBROBLAST-GROWTH-FACTOR-21; PROTEIN; OBESITY; PGC-1-ALPHA; STEATOSIS;

D O I：

10.1016/j.bbrc.2015.02.104

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Fibroblast growth factor 21 (FGF21) plays critical roles in regulating glucose and lipid metabolism. beta-Klotho is the co-receptor for mediating FGF21 signaling, and the mRNA levels of this receptor are increased in the liver of human subjects with obesity. However, the molecular mechanisms underlying the regulation of beta-klotho expression remain poorly defined. Here, we report that elevation of beta-klotho protein expression in diet-induced obese mice and human patients is associated with increased endoplasmic reticulum (ER) stress. In vivo study indicates that administration of the ER stressor tunicamycin in mice led to increased expression of beta-klotho in the liver. In addition, we show that ER stress is sufficient to potentiate FGF21 signaling in HepG2 cell and ATF4 signaling pathway is essential for mediating the effect of ER stress on beta-klotho expression. These findings demonstrate a link of ER stress with up-regulation of hepatic beta-klotho expression and the molecular mechanism underlying ER stress-regulated FGF21 signaling. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：300 / 305

页数：6

共 35 条

[1]

[Anonymous], 2015, INT J OBESITY, DOI DOI 10.1038/ijo.2014.76

[2]

Badman MK, 2007, CELL METAB, V5, P426, DOI 10.1016/j.cmet.2007.05.002

[3]

Protein Folding in the Endoplasmic Reticulum [J].