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

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.

Keywords: ETV5; Ghrelin; Ghrelin-O-Acyl-transferase; Transcription factor; mTOR signaling.