Small intestine barrier function failure induces systemic inflammation in monosodium glutamate-induced chronically obese mice

Abstract

Chronic obesity has increased worldwide, in conjunction with type 2 diabetes. Chronic obesity causes systemic inflammation that may result in functional deterioration of the gastrointestinal barrier. However, gastrointestinal conditions associated with chronic obesity have not been comprehensively investigated. The purpose of this study was to evaluate morphological changes in small intestine barrier structures during chronic obesity. A mouse model of chronic obesity induced by monosodium glutamate treatment was established. At postnatal week 15, pathological changes including in small intestinal epithelial cells were analyzed in chronically obese mice compared with controls. Numerous gaps were identified between small intestinal epithelial cells in chronically obese mice, and levels of both desmosomal and tight junction proteins were significantly lower in their small intestinal epithelial cells. Moreover, in chronically obese mice, a significant increase in the number of intestinal inflammatory cells, particularly macrophages, was observed; in addition, blood samples from the mouse model show an increase in markers of inflammation, tumor necrosis factor-alpha and interleukin-1-beta. These findings suggest that functional deterioration of adhesion structures between small intestinal epithelial cells causes gastrointestinal barrier function failure, leading to a rise in intestinal permeability to blood vessels and consequent systemic inflammation, characterized by macrophage infiltration.