ETV5 通过 mTORC1 依赖性方式调节 GOAT/ghrelin 系统。

ETV5 regulates GOAT/ghrelin system in an mTORC1-dependent manner.

机构信息

Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong province, 518000, China.

出版信息

Mol Cell Endocrinol. 2019 Apr 5;485:72-80. doi: 10.1016/j.mce.2019.02.003. Epub 2019 Feb 5.

DOI:10.1016/j.mce.2019.02.003

PMID:30735697

Abstract

Ghrelin, a 28 amino acid peptide hormone, regulates multiple important metabolic functions. Its acylation by ghrelin-O-acyl-transferase enzyme (GOAT) is required for binding to and activating its receptor, the growth hormone secretagogue receptor 1a. Mechanism underlying the regulation of GOAT and acyl ghrelin remains unclear. The present study demonstrated that ETV5 could transactivate GOAT promoter region and increase its expression, leading to subsequent increase in the production of acyl ghrelin. mTORC1 modulated ETV5 expression levels, likely via altering its protein stability, in the murine hypothalamic CLU122 cells and in mice. Moreover, ETV5 mediated the effects of mTORC1 signaling on the expression level of acyl ghrelin. Our study suggests a novel mTORC1-ETV5-GOAT/ghrelin axis in the regulation of ghrelin system. ETV5 may be a key regulator of mTORC1-GOAT/ghrelin axis in ghrelin producing cells and a potential therapeutic target for organism energy imbalance.

摘要

胃饥饿素是一种 28 个氨基酸的肽类激素，调节多种重要的代谢功能。其与生长激素促分泌素受体 1a 结合并激活该受体所必需的酰化由胃饥饿素-O-酰基转移酶（GOAT）酶完成。GOAT 和酰基胃饥饿素的调节机制尚不清楚。本研究表明，ETV5 可反式激活 GOAT 启动子区域并增加其表达，从而导致酰基胃饥饿素的产生增加。mTORC1 通过改变其蛋白稳定性来调节 CLU122 细胞和小鼠中 ETV5 的表达水平。此外，ETV5 介导了 mTORC1 信号对酰基胃饥饿素表达水平的影响。我们的研究表明，在胃饥饿素系统的调节中存在一个新的 mTORC1-ETV5-GOAT/ghrelin 轴。ETV5 可能是胃饥饿素产生细胞中 mTORC1-GOAT/ghrelin 轴的关键调节剂，也是机体能量失衡的潜在治疗靶点。