The association of gastric leptin with esophageal inflammation and metaplasia

Fritz Francois ^1*, Jatin Roper ¹, Adam Goodman ¹, Zhiheng Pei ¹, Muhammad Ghumman ¹, Michelle Mourad ², Asalia Z. Olivares de Perez ¹, Guillermo I. Perez-Perez ¹, Chi-Hong Tseng ¹ and Martin J. Blaser ¹

¹ NYU School of Medicine, United States
² University of California San Francisco, United States

^* To whom correspondence should be addressed. E-mail: fritz.francois{at}med.nyu.edu.

Accepted 14 August 2007

Abstract

Background Gastroesophageal reflux disease (GERD) complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence esophageal mucosal homeostasis.

Aims To determine whether leptin receptors are present in the esophagus, and whether serum or gastric leptin levels are associated with esophageal inflammation and metaplasia.

Methods From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal esophagus and serum samples were collected. Patients were classified as having normal, inflamed, or Barrett's esophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay.

Results Of 269 individuals enrolled, 105 were H. pylori-negative. Of the 88 patients with complete esophageal biopsies, 44 were normal, 24 were inflamed, and 20 were Barrett's esophagus. Receptors for leptin were highly expressed on esophageal epithelial cells with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p=0.01) higher fundic leptin levels [Median 202 pg/mg (IQR 123-333)] compared to normal [126 pg/mg (78-221)] or inflamed [114 pg/mg (76-195)] esophagus. In multivariate analysis, for every 2-fold increase in fundic leptin, the odds of having Barrett's was 3.4 times [95% CI 1.5-7.6] higher compared to having a normal esophagus.

Conclusions Leptin receptor expression on esophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential esophageal healing and metaplasia progression.

Keywords: Barrett esophagus, Gastroesophageal reflux, Inflammation, Leptin, Leptin receptor

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