Anti‐TNF Therapy Is Associated With Browning‐ and Immune‐Related Changes in Creeping Fat in Crohn's Disease
10 affiliations
- 1Hospital Universitari de Tarragona Joan XXIII Institut de Recerca Biomèdica Catalunya Sud (formerly Institut d’Investigació Sanitària Pere Virgili) Tarragona Spain
- 2Department of Biochemistry and Biotechnology Universitat Rovira i Virgili Tarragona Spain
- 3Department of Gastroenterology Hospital Universitari de Tarragona Joan XXIII Institut de Recerca Biomèdica Catalunya Sud Tarragona Spain
- 4Colorectal Surgery Unit Hospital Universitari de Tarragona Joan XXIII Institut de Recerca Biomèdica Catalunya Sud Tarragona Spain
- 5Department of Medicine and Surgery Universitat Rovira i Virgili Reus Spain
- 6Department of Pathology Hospital Universitari de Tarragona Joan XXIII Tarragona Spain
- 7Colorectal Surgery Unit Hospital de Sant Pau i Santa Tecla Institut de Recerca Biomèdica Catalunya Sud Tarragona Spain
- 8Department of General Surgery Colorectal Surgery Unit Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Barcelona Spain
- 9Institut de Recerca Germans Trias i Pujol (IGTP) Badalona Spain
- 10CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD) Instituto de Salud Carlos III Madrid Spain
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.
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BibTeX
@article{monfortferre2026antitnf,
title = {{Anti‐TNF Therapy Is Associated With Browning‐ and Immune‐Related Changes in Creeping Fat in Crohn's Disease}},
author = {Diandra Monfort‐Ferré and Iris Ginés and Claudia Cepero and Laia Cabré and Aledis Caro and Margarita Menacho and Miriam Gené and Montserrat Garcia and Maria del Carmen Lahoz and Maria José Mañas and Marc Martí and Aitana Tarzán and Roger Suau and Joan Ferreres and Josep Manyé and Carolina Serena},
journal = {United European Gastroenterology Journal},
year = {2026},
month = nov,
doi = {10.1002/ueg2.70320},
url = {https://doi.org/10.1002/ueg2.70320},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Anti‐TNF Therapy Is Associated With Browning‐ and Immune‐Related Changes in Creeping Fat in Crohn's Disease
AU - Diandra Monfort‐Ferré
AU - Iris Ginés
AU - Claudia Cepero
AU - Laia Cabré
AU - Aledis Caro
AU - Margarita Menacho
AU - Miriam Gené
AU - Montserrat Garcia
AU - Maria del Carmen Lahoz
AU - Maria José Mañas
AU - Marc Martí
AU - Aitana Tarzán
AU - Roger Suau
AU - Joan Ferreres
AU - Josep Manyé
AU - Carolina Serena
PY - 2026
DA - 2026/11/04
JO - United European Gastroenterology Journal
DO - 10.1002/ueg2.70320
UR - https://doi.org/10.1002/ueg2.70320
AB - 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.
SN - 2050-6406
SN - 2050-6414
ER -