High-Fat Diet Induces Disruption of the Tight Junction-Mediated Paracellular Barrier in the Proximal Small Intestine Before the Onset of Type 2 Diabetes and Endotoxemia

Autor(es)

Nascimento, J. C. ^[1] ; Matheus, V. A. ^[1] ; Oliveira, R. B. ^[1] ; Tada, S. F. S. ^[1] ; Collares-Buzato, Carla B. ^[1]

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Digestive Diseases and Sciences; v. 66, n. 10, p. 3359-3374, OCT 2021.
• Citações Web of Science: 3

Resumo

Background/Aim A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes. Methods/Results HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-alpha levels in plasma or adipose tissue, and in intestinal segments as compared to the controls. Conclusion Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability. (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