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

Area of Science:

• Gastroenterology
• Metabolic Diseases
• Cell Biology

Background:

• High-fat diets (HFD) alter the intestinal lumen environment.
• Gut dysbiosis and increased intestinal permeability are implicated in type 2 diabetes mellitus (T2DM) pathogenesis.
• Intestinal barrier disruption may trigger inflammation and insulin resistance.

Purpose of the Study:

• To investigate the effect of intestinal luminal content from HFD-fed mice on epithelial barrier function.
• To examine the impact on tight junction (TJ)-mediated epithelial barriers in Caco-2 and MDCK cells.

Main Methods:

• Isolated small and large intestine luminal content from control and HFD-fed prediabetic mice.
• Exposed Caco-2 and MDCK epithelial cell lines to luminal content.
• Measured transepithelial electrical resistance (TEER) and paracellular flux.
• Assessed TJ protein expression (claudins, occludin, ZO-1).

Main Results:

• Small intestine luminal content from HFD-fed mice significantly decreased TEER and increased paracellular flux, with reduced TJ proteins.
• Large intestine luminal content from HFD-fed mice increased paracellular flux and altered TJ protein distribution.
• These changes indicate disruption of the TJ barrier integrity.

Conclusions:

• Altered intestinal luminal components from HFD exposure impair TJ structure and function in vitro.
• This supports a role for the intestinal paracellular barrier in obesity-related T2DM pathogenesis.