Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats

Takuya Suzuki,Hiroshi Hara

doi:10.1186/1743-7075-7-19

Abstract

BackgroundAn increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability.MethodsAn obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF), and the lean counter strain, Long Evans Tokushima Otsuka (LETO), were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ) proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells.ResultsThe OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein) was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1) expression in the small, but not in the large intestine (cecum or colon). The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1) in the Caco-2 cell monolayers.ConclusionExcessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are responsible for the increase in small intestinal permeability resulting from the suppression of TJ protein expression.

Highlights

An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, the pathogenesis of the increase in the intestinal permeability is poorly understood
Oral glucose tolerance test (OGTT) The Otsuka Long Evans Tokushima Fatty (OLETF) rats showed higher glucose intolerance than did the Long Evans Tokushima Otsuka (LETO) rats, which became more marked with the prolonged feeding of the high fat diet (Fig. 1)
The present study demonstrated that obesity by itself did not increase intestinal permeability in OLETF rats, a genetic obesity and type 2 diabetes model, whereas the feeding of a high fat diet increased intestinal permeability in both OLETF and their lean counter strain, LETO, rats

Summary

Introduction

An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, the pathogenesis of the increase in the intestinal permeability is poorly understood. The high prevalence of obesity and type 2 diabetes is becoming a serious socioeconomic and clinical problem in developed countries [1]. Cani et al [4] demonstrated that feeding a high fat diet increased intestinal permeability in mice, which was normalized by simultaneous antibiotic treatment. They suggested that the high fat-induced changes in the gut microflora increased intestinal permeability. The pathogenesis of the increase in intestinal permeability in obesity remains controversial

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