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

Autor(es)

de Oliveira, Ricardo Beltrame ^[1] ; Matheus, Valquiria Aparecida ^[1] ; Canuto, Leandro Pereira ^[1] ; De Sant'ana, Ariane ^[1] ; Collares-Buzato, Carla Beatriz ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, UNICAMP, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 238, DEC 1 2019.
• Citações Web of Science: 0

Resumo

Aim: 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. Methods/key findings: 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. Significance: 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. (AU)

• Processo FAPESP: 18/02118-2 - Papel da barreira epitelial intestinal mediada pela junção de oclusão na patogênese da diabetes melito tipo 2 experimental e a repercussão da exposição ao butirato: estudos in vivo e in vitro.
• Beneficiário: Carla Beatriz Collares Buzato
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/15676-0 - Modulação in vitro da barreira epitelial intestinal mediada pelas junções de oclusão (tight junctions): efeito da exposição a nutrientes (glicose e ácidos graxos), à insulina, e à microflora bacteriana de animais pré-diabéticos
• Beneficiário: Carla Beatriz Collares Buzato
• Modalidade de apoio: Auxílio à Pesquisa - Regular