Ghrelin acylation by ghrelin-O-acyltransferase can occur in healthy part of oncologic liver in humans

INTRODUCTION: Activation of ghrelin is controlled by the enzyme Ghrelin-O-Acyl Transferase (GOAT). In humans, localization of this acylation is poorly understood. The aim of that study was to explore GOAT localization and activation in human Liver by evaluating both bioactive and non-bioactive ghrelin in the blood stream entering and leaving liver and to simultaneously evaluate GOAT mRNA expression in Liver. METHODS: Healthy part of oncologic hepatic tissue collected from nine patients undergoing hepatectomy was used to evaluate GOAT mRNA expression by quantitative real time polymerase chain reaction (RTqPCR). Simultaneously blood from portal vein, supra hepatic vein, sub clavicular vein and radial artery was also sampled to assay total and acylated ghrelin. RESULTS: Acylated ghrelin level was significantly increased in supra hepatic vein compared to portal vein level (385±42 ng/ml vs. 268±24 ng/ml, p=0.04). Supra hepatic vein to portal vein ratio for acylated ghrelin (acylation ratio) is at 1.4±0.1. Mean expression of GOAT mRNA in liver, expressed as 2-∆Ct/µg total RNA/1µl of liver tissue was at 0.042±0.021 arbitrary units. GOAT mRNA expression in liver was correlated with acylated to total ghrelin ratio in supra hepatic vein (p=0.016, R=0.75) and with acylation liver ratio (p=0.05, R=0.61). CONCLUSIONS: Blood concentration of acylated ghrelin was found significantly increased after its passage through liver suggesting acylation can occur in the liver. RTqPCR data confirmed the presence of GOAT in liver, with positive correlation between GOAT expression and acylated ghrelin liver ratio. This study strongly suggests that liver is a site of ghrelin acylation in human