Time-dependent alteration to the tight junction structure of distal intestinal epithelia in type 2 prediabetic mice

High-fat diet (HFD) intake has been associated with changes in intestinal microbiota composition, increased intestinal permeability, and onset of type 2 diabetes mellitus (T2DM). The aim of this work was twofold: 1) to investigate the structural and functional alterations of the tight junction (TJ)-...

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Veröffentlicht in:Life sciences (1973) 2019-12, Vol.238, p.116971-116971, Article 116971
Hauptverfasser: de Oliveira, Ricardo Beltrame, Matheus, Valquiria Aparecida, Canuto, Leandro Pereira, De Sant'ana, Ariane, Collares-Buzato, Carla Beatriz
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container_title Life sciences (1973)
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Matheus, Valquiria Aparecida
Canuto, Leandro Pereira
De Sant'ana, Ariane
Collares-Buzato, Carla Beatriz
description High-fat diet (HFD) intake has been associated with changes in intestinal microbiota composition, increased intestinal permeability, and onset of type 2 diabetes mellitus (T2DM). The aim of this work was twofold: 1) to investigate the structural and functional alterations of the tight junction (TJ)-mediated intestinal epithelial barrier of ileum and colon, that concentrate most of the microbiota, after exposure to a HFD for 15, 30 and 60 days, and 2) to assess the effect of in vitro exposure to free fatty acids (FFAs), one of the components of HFD, on paracellular barrier of colon-derived Caco-2 cells. HFD exposure induced progressive metabolic changes in male mice that culminated in prediabetes after 60d. Morphological analysis of ileum and colon mucosa showed no signs of epithelial rupture or local inflammation but changes in the junctional content/distribution and/or cellular content of TJ-associated proteins (claudins-1, -2, -3, and occludin) in intestinal epithelia were seen mainly after a prediabetes state has been established. This impairment in TJ structure was not associated with significant changes in intestinal permeability to FITC-dextran. Exposure of Caco-2 monolayers to palmitic or linoleic acids seems to induce a reinforcement of TJ structure while treatment with oleic acid had a more diverse effect on TJ protein distribution. TJ structure in distal intestinal epithelia can be specifically impaired by HFD intake at early stage of T2DM, but not by FFAs in vitro. Since the TJ change in ileum/colon was marginal, probably it does not contribute to the disease onset.
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Exposure of Caco-2 monolayers to palmitic or linoleic acids seems to induce a reinforcement of TJ structure while treatment with oleic acid had a more diverse effect on TJ protein distribution. TJ structure in distal intestinal epithelia can be specifically impaired by HFD intake at early stage of T2DM, but not by FFAs in vitro. 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Exposure of Caco-2 monolayers to palmitic or linoleic acids seems to induce a reinforcement of TJ structure while treatment with oleic acid had a more diverse effect on TJ protein distribution. TJ structure in distal intestinal epithelia can be specifically impaired by HFD intake at early stage of T2DM, but not by FFAs in vitro. 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Exposure of Caco-2 monolayers to palmitic or linoleic acids seems to induce a reinforcement of TJ structure while treatment with oleic acid had a more diverse effect on TJ protein distribution. TJ structure in distal intestinal epithelia can be specifically impaired by HFD intake at early stage of T2DM, but not by FFAs in vitro. Since the TJ change in ileum/colon was marginal, probably it does not contribute to the disease onset.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>31634462</pmid><doi>10.1016/j.lfs.2019.116971</doi><tpages>1</tpages></addata></record>
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subjects Animals
Caco-2 Cells
Colon
Dextran
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Experimental - etiology
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Type 2 - etiology
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Diet, High-Fat - adverse effects
Exposure
Fatty acids
Free fatty acids
High fat diet
Humans
Ileum
Intestinal epithelial barrier
Intestinal microflora
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Intestine
Male
Mice
Mice, Inbred C57BL
Microbiota
Mucosa
Occludin
Oleic acid
Paracellular permeability
Permeability
Prediabetic State - etiology
Prediabetic State - metabolism
Prediabetic State - pathology
Protein structure
Proteins
Structure-function relationships
Tight junction
Tight Junction Proteins - metabolism
Tight Junctions - metabolism
Tight Junctions - pathology
Time dependence
Time Factors
Type 2 diabetes mellitus
title Time-dependent alteration to the tight junction structure of distal intestinal epithelia in type 2 prediabetic mice
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