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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Oliveira, R. B. [1] ; Canuto, L. P. [1] ; Collares-Buzato, C. B. [1]
Total Authors: 3
[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Life Sciences; v. 216, p. 10-21, JAN 1 2019.
Web of Science Citations: 4

Aims: Evidence suggests that administration of a high-fat diet (HFD) results in changes in the intestinal lumen environment. Gut dysbiosis associated with intestinal barrier disruption may be involved in type 2 diabetes mellitus (T2DM) development through increased intestinal permeability, which would trigger an inflammatory response leading to peripheral insulin resistance state and ultimately T2DM. 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 findings: Exposure 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. Significance: Luminal 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 obesityrelated T2DM pathogenesis. (AU)

FAPESP's process: 18/02118-2 - Role of the tight junction-mediated intestinal epithelial barrier in the pathogenesis of type 2 diabetes mellitus and the effect of butyrate treatment using in vivo and in vitro models.
Grantee:Carla Beatriz Collares Buzato
Support Opportunities: Regular Research Grants
FAPESP's process: 13/15676-0 - In vitro modulation of intestinal epithelial barrier mediated by tight junctions: effect of exposure to nutrients (glucose and fatty acids), insulin and bacterial microbiota of prediabetic animals
Grantee:Carla Beatriz Collares Buzato
Support Opportunities: Regular Research Grants