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Poster De Conférence Année : 2013

Progressive increase in large intestine transcellular but not paracellular permeability correlates with plasma endotoxemia in diet-induced obese rats

Résumé

Background: High fat diet-induced obesity is characterized by increased intestinal paracellular permeability, increased plasma lipopolysaccharide (LPS), low-grade inflammation and metabolic alterations. Whether the increase in plasma LPS is due to the increased paracellular permeability is unclear. Moreover, the contribution of altered paracellular versus transcellular transport in different regions of the intestine to the obese phenotype has not been determined. Since LPS is a large molecule (.10 kDa), we hypothesized that it crosses the epithelium via a transcellular route. The aims of this study aims were to determine 1) the route of LPS passage and 2) the temporal relationship between alterations in small and large intestinal permeability and endotoxemia in rats fed a high fat diet. Methods: Route of LPS passage was evaluated in cell culture models (Caco-2 and T84) and in rat intestinal tissues mounted in Ussing chambers using LPS-FITC, horseradish peroxidase (HRP, marker of transcellular permeability) and electrical conductance (marker of paracellular permeability). Diet-induced obesity was induced by feeding rats a high fat diet (HF, 45% fat) or normal chow (NC, 10% fat) for 1, 3 or 6 weeks. FITC-dextran 4000 (FD-4, marker of paracellular permeability) and HRP fluxes across intestinal tissues were evaluated in Ussing chambers. Plasma LPSbinding protein (LBP) was measured by ELISA. Results: In Caco-2 and T84 cells and rat intestine, FITC-LPS flux correlated significantly with HRP flux (P ,0.05) but not with electrical conductance (P.0.05), suggesting LPS crosses the gut epithelium through the transcellular rather than paracellular route. In the small intestine, FD-4 flux was higher in HF than NC rats at wk1 (jejunum P=0.08, ileum P=0.004) then returned to normal values ; HRP flux was not affected by HF diet (Table 1). In the large intestine, FD-4 flux was increased in the HF rats (Table 1). HRP flux was increased in the caecum and colon of HF compared to NC rats at wk3 (P=0.03 and 0.04) and wk6 (P=0.009 and 0.02) but not wk1 (Table 1). Plasma LBP was increased in HF rats at wk3 and wk6 (P=0.03 and 0.04, Table 1). Plasma LBP significantly correlated with caecum and colon HRP flux (P=0.006 and 0.01), which correlated significantly with adiposity (P,0.001). Conclusion: HF feeding induces an early increase in paracellular permeability in both small and large intestine. HF feeding induces a later onset (wk3) increase in transcellular transport in the large intestine that correlates with plasma LBP and adiposity. These data support the hypothesis that alteration of transcellular but not paracellular transport in the large intestine is involved in the metabolic endotoxemia and phenotype of diet-induced obesity in rats.
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hal-01594350 , version 1 (26-09-2017)

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Gaëlle Boudry, M Kristina Hamilton, Guillaume de Lartigue, Charlotte Ronveaux, Helen E Raybould. Progressive increase in large intestine transcellular but not paracellular permeability correlates with plasma endotoxemia in diet-induced obese rats. Digestive disease week, May 2013, Orlando, United States. Gastroenterology, 144 (5) (Suppl.1), 2013, Gastroenterology. ⟨10.1016/S0016-5085(13)60453-9⟩. ⟨hal-01594350⟩
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