The Porcine Colitis Model Recapitulates the Visceral Adipose Metabolic Reprogramming of Human Ulcerative Colitis.

Area of Science:

• Immunometabolism
• Gastroenterology
• Comparative Biology

Background:

• Adipose tissue dysfunction is key in ulcerative colitis (UC) pathophysiology.
• Understanding cross-species adipose immunometabolic responses in UC is crucial.

Purpose of the Study:

• To compare adipose remodeling and immunometabolic responses in porcine and murine colitis models with human UC data.
• To investigate species-specific differences in adipose tissue response to intestinal inflammation.

Main Methods:

• Comparative transcriptomic analysis of adipose tissue.
• Dextran sulfate sodium (DSS)-induced colitis models in pigs and mice.
• Analysis of human UC patient datasets.

Main Results:

• Intestinal inflammation caused adipocyte atrophy and convergent inflammatory responses in visceral and subcutaneous fat.
• A systemic suppression of fatty acid synthesis pathways was observed, correlating negatively with colitis severity.
• Murine visceral fat showed fatty acid metabolism activation, while porcine fat mirrored human UC downregulation of fatty acid metabolism.

Conclusions:

• A fundamental species-specific difference exists in adipose tissue response to intestinal inflammation.
• The porcine model accurately replicates human UC-associated adipose atrophy and suppressed fatty acid metabolism.
• The porcine model serves as a valuable translational tool for studying inflammatory bowel disease.