Ghrelin is a multifunctional gut peptide with a unique structure, which is modified by a medium chain fatty acid at the third serine by ghrelin O-acyl transferase (GOAT). It is well known that the major source of plasma ghrelin is the stomach, but the transcriptional regulation of gastric ghrelin and GOAT is incompletely understood. Here, we studied the involvement of the nuclear receptors REV-ERBα and REV-ERBβ on ghrelin and GOAT gene expression in vivo and in vitro. Reverse-transcriptase polymerase chain reaction analysis showed that REV-ERBα and REV-ERBβ mRNAs were expressed in the stomach and a stomach-derived ghrelin cell line (SG-1 cells). In vivo experiments with mice revealed the circadian rhythm of ghrelin, GOAT, and REV-ERBs. The peak expression of ghrelin and GOAT mRNAs occurred at Zeitgeber time (ZT) 4, whereas that of REV-ERBα and REV-ERBβ was observed at ZT8 and ZT12, respectively. Treatment of SG-1 cells with SR9009, a REV-ERB agonist, led to a significant reduction in ghrelin and GOAT mRNA levels. Overexpression of REV-ERBα and REV-ERBβ decreased ghrelin and GOAT mRNA levels in SG-1 cells. In contrast, small-interfering RNA (siRNA)-mediated double-knockdown of REV-ERBα and REV-ERBβ in SG-1 cells led to the upregulation in the expression of ghrelin and GOAT mRNAs. These results suggest that REV-ERBs suppress ghrelin and GOAT mRNA expression.

Ghrelin 是一种具有独特结构的多功能肠肽，其由 ghrelin O-酰基转移酶 (GOAT)在第三个丝氨酸处由中链脂肪酸修饰。众所周知，血浆 ghrelin 的主要来源是胃，但胃 ghrelin 和 GOAT 的转录调控尚不完全清楚。在这里，我们研究了核受体 REV-ERBα 和 REV-ERBβ在体内和体外对ghrelin和GOAT基因表达的参与。逆转录酶聚合酶链反应分析表明，REV-ERBα和REV-ERBβ mRNA 在胃和胃来源的 ghrelin 细胞系（SG-1 细胞）中表达。小鼠体内实验揭示了生长素释放肽、GOAT 和 REV-ERB 的昼夜节律。ghrelin和GOAT mRNA的峰值表达发生在 Zeitgeber 时间 (ZT) 4，而REV-ERBα和REV-ERBβ的峰值表达分别在 ZT8 和 ZT12 观察到。用 REV-ERB 激动剂 SR9009 处理 SG-1 细胞导致ghrelin和GOAT mRNA 水平显着降低。REV-ERBα 和 REV-ERBβ 的过表达降低了 SG-1 细胞中的ghrelin和GOAT mRNA 水平。相反，小干扰 RNA (siRNA) 介导的 SG-1 细胞中 REV-ERBα 和 REV-ERBβ 的双重敲低导致生长素释放肽和山羊mRNA。这些结果表明 REV-ERB 抑制ghrelin和GOAT mRNA 表达。