Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet

The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.

Automated summary

The impact of a high-fat diet on intestinal permeability is well documented, but the exact mechanism behind leaky gut caused by an HFD is unclear. In this study, researchers investigated the mechanism underlying HFD-induced leaky gut and found an increase in fat accumulation in the liver and a trend towards increased intestinal permeability in mice fed an HFD. Proteomics analysis revealed differentially expressed proteins related to endocytosis, protein transport, and tight junctions in the small intestine epithelial cells. The study also identified a correlation between the expression of Cldn7 and intestinal barrier function, as well as its strong correlation with Epcam.