Intestinal luminal content from high-fat-fed prediabetic mice changes epithelial barrier function in vitro

In this study, we investigated the effect of the intestinal luminal content isolated from control or HFD-fed prediabetic mice upon the tight junction (TJ)-mediated epithelial barrier in Caco-2 and MDCK epithelial cell lines.Methods/key findingsExposure to small intestine luminal content (SI) isolated from HFD-fed prediabetic mice induced a more significant decrease in transepithelial electrical resistance (TEER), associated with higher paracellular flux in Caco-2 and MDCK cells after 6 h and 4 h respectively, as compared to the SI obtained from control mice. Such changes were accompanied by a significant decrease in TJ content of claudins, occludin, and ZO-1, indicative of disruption of the TJ barrier. Meanwhile, large intestine luminal content from control (Ctrl-LI) and prediabetic (HFD-LI) animals did not change TEER significantly, however, paracellular flux was significantly increased after 24 h, accompanied by a decrease in ZO-1 (after HFD-LI exposure) in Caco-2 and significant changes in the junctional distribution of claudins-1, -2, occludin and ZO-1 proteins in MDCK, particularly after HFD-LI exposure.SignificanceLuminal components of intestinal content, altered by HFD exposure, induce impairment of the TJ structure and function in vitro, corroborating the idea of a role of the intestinal paracellular barrier in the obesity-related T2DM pathogenesis.
Source: Life Sciences - Category: Biology Source Type: research