Patient-derived colon epithelial organoids reveal lipid-related metabolic dysfunction in pediatric ulcerative colitis.

ABSTRACT: Ulcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Here, we develop colon organoid (colonoid) lines from pediatric patients with endoscopically active UC, inactive UC, and those without intestinal inflammation to interrogate functional metabolic differences in the colon epithelia. We demonstrate that active UC colonoids exhibit hypermetabolic features and cellular stress, specifically during differentiation. Hypermetabolism in active UC colonoids is driven, in part, by increased proton leak, and excess lipid accumulation. Active UC colonoids exhibit heightened activation of the master lipid regulator PPAR-α and its transcriptional pathways. Pharmacological PPAR-α inhibition limits lipid accumulation, induces a metabolic shift tow

SUBMITTER: Ojo BA 

PROVIDER: S-EPMC12695892 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature