Cathelicidin-WA Facilitated Intestinal Fatty Acid Absorption Through Enhancing PPAR-γ Dependent Barrier Function

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Cellular uptake and regulation of long-chain fatty acids (LCFA) are critical for intestinal function but remain incompletely understood.
• Intestinal barrier dysfunction, often induced by factors like Lipopolysaccharide (LPS), can impair nutrient absorption, including fatty acids.

Purpose of the Study:

• To investigate the role of Cathelicidin-WA (CWA) in modulating intestinal fatty acid uptake and barrier function.
• To elucidate the molecular mechanisms, particularly the involvement of peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling, underlying CWA's effects.

Main Methods:

• Establishment of an intestinal barrier dysfunction model using LPS in mice and Caco2 cells.
• Evaluation of LCFA uptake capacity and intestinal barrier integrity.
• Assessment of CWA's effects on LCFA absorption and barrier function, with and without PPAR-γ inhibition.

Main Results:

• LPS stimulation impaired intestinal LCFA absorption, while CWA pretreatment restored it.
• CWA's beneficial effects on LCFA absorption were dependent on CD36 and FABP4, but not FABP.
• CWA enhanced intestinal barrier function against LPS-induced damage, a process dependent on intact PPAR-γ signaling.

Conclusions:

• CWA facilitates intestinal LCFA absorption and strengthens barrier function by activating PPAR-γ signaling.
• PPAR-γ is a key mediator of CWA's protective effects against LPS-induced intestinal dysfunction.
• CWA shows potential as a therapeutic agent to address fatty acid malabsorption and strengthen intestinal barrier integrity.