ArticleGastroenterology2025
Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.
Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study.bioRxiv : the preprint server for biology · 2026Article
- Review
- Dual-energy computed tomography quantification of creeping fat in Crohn's disease: A new radiologic biomarker for transmural disease monitoring.World journal of radiology · 2026Article
- Mesenteric Adipose Tissue as a Modulator of Intestinal Inflammation: Mechanistic Insights and Model Systems in Crohn's Disease.European journal of immunology · 2026Review
- Mesenteric adipose tissue: from protective gatekeeper to driver of inflammatory bowel disease.Immunometabolism (Cobham, Surrey) · 2026Review
- Tissue-layer-resolved proteome landscape of Crohn's disease strictures highlights potential drivers of fibrosis progression.JCI insight · 2026Article
- The role of lipid metabolism and creeping fat in disease assessment and prediction for Crohn's disease.Frontiers in immunology · 2026Review
- Cardiovascular risk in inflammatory bowel disease: focus on lipids and visceral adipose tissue.Frontiers in endocrinology · 2026Review
- T-cadherin as a potential novel regulator of intestinal inflammation and fibrosis.Frontiers in physiology · 2026Review
- Elucidating a Myofibroblast-dominated Fibrotic Niche in Crohn's Disease-associated Fibrostenosis Through High-resolution Spatial Transcriptomics.Cellular and molecular gastroenterology and hepatology · 2026Article
- Quantification of visceral adipose tissue volume predicts both short-term and long-term transmural healing in patients with Crohn's disease receiving Ustekinumab.Therapeutic advances in gastroenterology · 2026Article
- Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?Annals of medicine · 2025Review
- Can Creeping Fat Be a Prognostic Factor in Crohn's Disease?The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Gut Microbiota as a Mediator Between Intestinal Fibrosis and Creeping Fat in Crohn's Disease.United European gastroenterology journal · 2025Review
- Obesity-Mediated Inflammation and Its Influence on Inflammatory Bowel Disease: Pathophysiology, Clinical Impact, and Therapeutic Implications.Biomolecules · 2025Review
- Preventing fibrosis in IBD: update on immune pathways and clinical strategies.Expert review of clinical immunology · 2024Review
- Intestinal strictures in Crohn's disease: An update from 2023.United European gastroenterology journal · 2024Review
- Creeping Fat in Crohn's Disease-Surgical, Histological, and Radiological Approaches.Journal of personalized medicine · 2023Review
- Cellular and Molecular Mechanisms of Intestinal Fibrosis.Gut and liver · 2023Review
- Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.Journal of Crohn's & colitis · 2021Article
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Authors and funding
37 authors.
Funding
Abstract
BACKGROUND &
aimsIn Crohn's disease, wrapping of mesenteric fat around the bowel wall, so-called "creeping fat," is highly associated with strictures. The strongest contributor to luminal narrowing in strictures is a thickening of the human intestinal muscularis propria (MP). We investigated creeping fat-derived factors and their effect on mechanisms of human intestinal MP smooth muscle cell (HIMC) hyperplasia.
methodsFree fatty acids (FFAs) in creeping fat or noncreeping mesenteric fat organ cultures were measured via lipidomic mass spectrometry. Primary HIMCs were exposed to FFAs and cell proliferation was assessed. Intracellular FFA metabolism pathways and reactive oxygen species were functionally evaluated. Muscle thickness was investigated in dextran sodium sulfate colitis with small molecule inhibition of FFA transport and a novel fat deletion mouse model.
resultsSubserosal creeping fat is associated with a markedly thickened MP. Experimental deletion of mesenteric fat (FAT-ATTAC [fat apoptosis through targeted activation of caspase 8] mouse) reduced MP thickness. Human creeping fat-conditioned medium strongly up-regulated HIMC proliferation. Creeping fat released higher amounts of 5 long-chain FFAs, including palmitate. Inhibition of HIMC long-chain FFA metabolism or FFA uptake into mitochondria through carnitine palmitoyltransferase-1 reduced the palmitate-induced HIMC proliferation. Blockade of conversion of palmitate into phospholipids reduced HIMC proliferation. Prophylactic inhibition of carnitine palmitoyltransferase-1 in experimental dextran sodium sulfate colitis did not ameliorate inflammation, but reduced MP thickness.
conclusionsCreeping fat-released long-chain FFAs induce a selective proliferative response by HIMC. These results point to creeping fat as a novel contributor to stricture formation in Crohn's disease.
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