Abstract：
Liver-expressed antimicrobial peptide 2 (LEAP2) and ghrelin have reciprocal effects on their common receptor, the growth hormone secretagogue receptor (GHSR). Ghrelin is considered a gastric hormone and LEAP2 a liver-derived hormone and both have been proposed to be involved in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated the mRNA expression of LEAP2, ghrelin and GHSR along the intestinal tract of individuals with and without TD2, and in the liver of men with and without obesity. Mucosal biopsies retrieved with 30-cm intervals throughout the small intestine and from 7 well-defined locations along the large intestine from 12 individuals with T2D and 12 healthy controls together with liver biopsies from 15 men with obesity and 15 lean men were subjected to bulk transcriptomics analysis. Both in individuals with and without T2D, mRNA expression of LEAP2 increased through the small intestine until dropping at the ileocecal valve, with little LEAP2 mRNA expression in the large intestine. Pronounced LEAP2 expression was observed in the liver of men with and without obesity. Robust ghrelin mRNA expression was observed in the duodenum of individuals with and without T2D, gradually decreasing along the small intestine with little expression in the large intestine. Ghrelin mRNA expression was not detected in the liver biopsies, and GHSR mRNA expression was not. In conclusion, we provide unique mRNA expression profiles of LEAP2, ghrelin and GHSR along the human intestinal tract showing no T2D-associated changes, and in the liver showing no differences between men with and without obesity.
摘要：
肝脏表达的抗菌肽2（LEAP2）和ghrelin对其共同受体有相互作用，生长激素促分泌素受体(GHSR)。Ghrelin被认为是胃激素，LEAP2被认为是肝脏衍生的激素，两者都被认为与肥胖和2型糖尿病（T2D）的病理生理学有关。我们调查了患有和不患有TD2的个体的肠道以及患有和不患有肥胖症的男性的肝脏中LEAP2，ghrelin和GHSR的mRNA表达。对来自12名T2D个体和12名健康对照者的小肠和沿着大肠的7个明确定义的位置以30-cm间隔检索的粘膜活检以及来自15名肥胖男性和15名瘦男性的肝活检进行批量转录组学分析。无论是在有和没有T2D的个体中，LEAP2的mRNA表达通过小肠增加，直到在回盲瓣下降，大肠中LEAP2mRNA表达很少。在有和没有肥胖的男性的肝脏中观察到明显的LEAP2表达。在有和没有T2D的个体的十二指肠中观察到健壮的ghrelinmRNA表达,沿着小肠逐渐减少，在大肠中几乎没有表达。在肝活检中未检测到GhrelinmRNA表达，而GHSRmRNA无表达。总之,我们提供了LEAP2，ghrelin和GHSR沿着人类肠道的独特mRNA表达谱，显示没有T2D相关的变化，在肝脏中，有肥胖和没有肥胖的男性之间没有差异。
