Work

Anti‐TNF Therapy Is Associated With Browning‐ and Immune‐Related Changes in Creeping Fat in Crohn's Disease

Year: 2026

Type: article

Abstract: BACKGROUND: Creeping fat (CrF) in Crohn's disease (CD) is a metabolically active perilesional adipose tissue involved in intestinal inflammation. Whether biological therapies modify its browning-associated phenotype remains largely unexplored. We investigated whether anti-TNF treatment is associated with changes in browning-, mitochondrial biogenesis- and immune-related pathways in CrF and whether similar molecular changes occur following ex vivo infliximab exposure. METHODS: Two independent human cohorts were analysed. (1) Observational cohort: CrF biopsies from anti-TNF-treated and anti-TNF-naïve CD patients (n = 14 and n = 19, respectively) were analysed for metabolic and inflammatory gene and protein expression. AdMSCs and mature CrF-derived adipocytes were isolated, and UCP1 protein abundance was assessed by immunohistochemistry and western blotting. (2) Ex vivo cohort: Paired CrF explants from anti-TNF-naïve patients with CD undergoing surgery were cultured with or without infliximab (5 mg/kg-equivalent, 24 h) and analysed by RT-qPCR and immunohistochemistry. RESULTS: Anti-TNF-treated patients showed higher UCP1 expression in CrF at mRNA and protein levels. CrF-derived mature adipocytes from treated patients exhibited increased expression of browning-/thermogenesis- and mitochondrial biogenesis-associated genes, together with reduced selected pro-inflammatory markers. AdMSCs also showed exploratory differences in their conditioned-medium protein profile, although no protein remained significant after FDR correction. Ex vivo infliximab exposure was associated with changes in selected browning-, mitochondrial biogenesis- and immune-related markers. DISCUSSION: Together, the observational and ex vivo findings identify CrF as an anti-TNF-responsive immunometabolic compartment in CD, characterised by coordinated browning-, mitochondrial biogenesis- and immune-related molecular changes. Functional studies are needed to establish the metabolic significance of these changes.

Source: United European Gastroenterology Journal

DOI: 10.1002/ueg2.70320