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

Abstract

Adipose tissue dysfunction is integral to the pathophysiology of ulcerative colitis (UC), yet the conservation of adipose immunometabolic responses across species remains unclear. Here, we employed a comparative transcriptomic approach to analyze adipose remodeling in dextran sulfate sodium (DSS)-induced porcine and murine colitis models alongside human UC datasets. We report that intestinal inflammation induced widespread adipocyte atrophy and triggered a convergent inflammatory response across physiologically distinct visceral and subcutaneous depots. Mechanistically, this remodeling was defined by a systemic suppression of fatty acid synthesis pathways. Importantly, the expression levels of key lipogenic enzymes were negatively correlated with the severity of colonic inflammation, indicating that intestinal injury directly dictates the magnitude of lipogenesis inhibition. Cross-species alignment revealed a critical distinction: while murine visceral fat exhibited fatty acid metabolism activation, the porcine response mirrored the fatty acid metabolism downregulation observed in human patients. These results identify a fundamental species-specific difference and establish the porcine model as a translational tool, which faithfully replicates the atrophy and fatty acid metabolism suppression characteristic of human inflammatory bowel disease.