기능성 소화불량증 환자에서의 Ghrelin과 Leptin의 발현

Abstract

Background and aims: Ghrelin and leptin have been indicated one of the etiological factors in functional dyspepsia (FD). In spite of several studies, the association between plasma ghrelin level and FD still remains controversial. Furthermore, only a few studies about leptin in FD have been introduced. We compared the major two forms of plasma ghrelin, serum leptin and gastric mRNA expression of both hormones between FD and control patients to understand underlying pathophysiology of FD. Methods: In total, two hundred and thirty two subjects (FD, n = 129 and healthy control, n = 103), who had undertaken endoscopy in Seoul National University Bundang Hospital from January 2011 to March 2013 were enrolled. FD patients were classified into two groups according to Rome III classification

postprandial distress syndrome (PDS, n = 88) and epigastric pain syndrome (EPS, n = 41). Self-reported questionnaire regarding FD, GERD and IBS symptoms was used. Acyl, des-acyl ghrelin and leptin levels in the fasting blood samples before endoscopy and mRNA expression of preproghrelin and leptin in the body mucosal tissue were measured by ELISA method and real time PCR, respectively. Results: Plasma acyl ghrelin was lower in PDS than in control and EPS (control: 13.0, PDS: 8.6, EPS: 13.9 fmol/ml, P < 0.001), while plasma des-acyl ghrelin, leptin and gastric mRNA expression of preproghrelin did not show any significant difference. Gastric leptin mRNA was significantly higher in patients with postprandial fullness (without fullness: 1.28, fullness: 1.80 P = 0.040). mRNA expression of preproghrelin of H. pylori (HP) positive patients (HP-positive: 0.70, HP-negative: 3.05, P < 0.001) was lower than the others but this does not lead to decrease in circulating ghrelin level. Women with HP infection had relatively higher expression of leptin mRNA than the others (HP-negative: 0.62, HP-positive: 1.45, P = 0.044). Conclusions: Plasma acyl ghrelin can play a certain role for development of PDS. However, it might be determined by not reducing mRNA expression but using posttranslational mechanism. On the other hand, elevated gastric leptin mRNA may cause gastric dysmotility and postprandial fullness. While HP infection with active or atrophic gastritis may reduce expression of preproghrelin mRNA, it can cause increase in expression of leptin mRNA by active gastritis.