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Fibrostenosing Crohn's disease (CD) represents a challenging clinical condition characterized by the development of symptomatic strictures within the gastrointestinal tract. Despite therapeutic advancements in managing inflammation, the progression of fibrostenotic complications remains a significant concern, often necessitating surgical intervention. Recent investigations have unveiled the pivotal role of smooth muscle cell hyperplasia in driving luminal narrowing and clinical symptomatology. Drawing parallels to analogous inflammatory conditions affecting other organs, such as the airways and blood vessels, sheds light on common underlying mechanisms of muscular hyperplasia. This review synthesizes current evidence to elucidate the mechanisms underlying smooth muscle cell proliferation in CD-associated strictures, offering insights into potential therapeutic targets. By highlighting the emerging significance of muscle thickening as a novel therapeutic target, this review aims to inform future research endeavors and clinical strategies with the goal to mitigate the burden of fibrostenotic complications in CD and other conditions. [ABSTRACT FROM AUTHOR]

This document is a commentary on a rapid action plan to improve the diagnosis and management of lipodystrophy syndromes. Lipodystrophy syndromes are rare conditions characterized by the loss of fat in the body, which can be genetic or acquired. The document discusses the challenges in diagnosing these syndromes and the importance of early detection for effective treatment. It also explores the relationship between lipodystrophy and other concomitant diseases, such as neurological disorders and autoimmune conditions. The ultimate goal of the rapid action plan is to improve diagnosis and treatment outcomes for patients with lipodystrophy syndromes. Additionally, the document discusses the connection between lipodystrophy syndromes and Crohn's disease, highlighting the association between lipodystrophy and "creeping fat" in Crohn's disease. Two case reports in 2019 showed the link between lipodystrophy syndromes and Crohn's disease, including bowel perforation and inflammation. The document suggests further research is needed to understand the molecular basis of this relationship and emphasizes the importance of considering the role of adipose tissue in concomitant conditions. [Extracted from the article]

Background & Aims: In 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., Methods: Free 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., Results: Subserosal 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., Conclusions: Creeping 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., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)