Effects of Central Obesity on Esophageal Epithelial Barrier Function

Abstract

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity−/GER–, Obesity+/GER−, Obesity−/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER− group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity−/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

Obesity and its effects on the esophageal mucosal barrier

“…Moreover, the esophageal intercellular space widths and desmosome densities of the obese patients with normal acid reflux did not differ significantly from those of patients with abnormal acid reflux, both obese and nonobese, suggesting that the esophageal barrier defects associated with visceral obesity alone are similar in severity to those associated with GERD. Using confocal laser endomicroscopy, the investigators found similar significant degrees of fluid leakage from esophageal epithelial capillaries for the obese patients without reflux and both groups of reflux patients, but not for the non-obese patients without reflux (50). These findings demonstrate that visceral obesity, independent of reflux, is associated with reduced cell adhesion proteins, dilation of intracellular spaces, and impaired esophageal mucosal barrier integrity.…”

“…TEM studies performed on esophageal biopsies from the four patient groups described by Blevins et al measured intercellular space width and desmosome density for cells of the stratum basalis (49,50). Compared with nonobese patients with normal acid reflux, the patients with visceral obesity and normal acid reflux had significantly wider mean intercellular spaces and significantly lower desmosome densities (50).…”

“…TEM studies performed on esophageal biopsies from the four patient groups described by Blevins et al measured intercellular space width and desmosome density for cells of the stratum basalis (49,50). Compared with nonobese patients with normal acid reflux, the patients with visceral obesity and normal acid reflux had significantly wider mean intercellular spaces and significantly lower desmosome densities (50). Moreover, the esophageal intercellular space widths and desmosome densities of the obese patients with normal acid reflux did not differ significantly from those of patients with abnormal acid reflux, both obese and nonobese, suggesting that the esophageal barrier defects associated with visceral obesity alone are similar in severity to those associated with GERD.…”

High Visceral-To-Subcutaneous Fat Ratio Is Associated with an Increased Risk of Gastroesophageal Reflux Disease in Nonobese Adults

“…Visceral adipose tissue produces pro-inflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor and adipokines such as leptin (which increases in obesity) and adiponectin (which decreases in obesity) [24][25][26]. Recent studies have suggested that visceral obesity, independent of reflux, is associated with dilatation of intracellular spaces and impaired esophageal mucosal barrier integrity [27,28]. Furthermore, these cytokines released from visceral fat may influence metaplasia of the esophagus, which affects carcinogenesis [29,30].…”

Recent advances in the epithelial barrier theory

“…Obesity is also an important condition in this group. Obesity impairs the structural and functional integrity of the oesophageal barrier, leading to oesophageal injury ( 169 ). A high-calorie and fat-enriched diet affects gut permeability and TJ restructuring in the mouse model ( 170 ).…”