Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece.
Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece.
Inflamm Bowel Dis. 2023 Nov 2;29(11):1826-1836. doi: 10.1093/ibd/izad095.
Although the phenomenon of hypertrophied adipose tissue surrounding inflamed bowel segments in Crohn's disease has been described since 1932, the mechanisms mediating the creeping fat formation and its role in the pathogenesis of the disease have not been fully unraveled. Recent advances demonstrating the multiple actions of adipose tissue beyond energy storage have brought creeping fat to the forefront of scientific research. In Crohn's disease, dysbiosis and transmural injury compromise the integrity of the intestinal barrier, resulting in an excessive influx of intraluminal microbiota and xenobiotics. The gut and peri-intestinal fat are in close anatomic relationship, implying a direct reciprocal immunologic relationship, whereas adipocytes are equipped with an arsenal of innate immunity sensors that respond to invading stimuli. As a result, adipocytes and their progenitor cells undergo profound immunophenotypic changes, leading to adipose tissue remodeling and eventual formation of creeping fat. Indeed, creeping fat is an immunologically active organ that synthesizes various pro- and anti-inflammatory cytokines, profibrotic mediators, and adipokines that serve as paracrine/autocrine signals and regulate immune responses. Therefore, creeping fat appears to be involved in inflammatory signaling, which explains why it has been associated with a higher severity or complicated phenotype of Crohn's disease. Interestingly, there is growing evidence for an alternative immunomodulatory function of creeping fat as a second barrier that prevents an abnormal systemic inflammatory response at the expense of an increasingly proliferating profibrotic environment. Further studies are needed to clarify how this modified adipose tissue exerts its antithetic effect during the course of Crohn's disease.
尽管自 1932 年以来就已经描述了克罗恩病中炎症性肠段周围肥大脂肪组织的现象，但介导 creeping fat 形成的机制及其在疾病发病机制中的作用尚未完全阐明。最近的进展表明，脂肪组织除了储存能量之外，还有多种作用，这使得 creeping fat 成为科学研究的前沿。在克罗恩病中，菌群失调和跨壁损伤破坏了肠道屏障的完整性，导致腔内微生物群和外源性物质的过度涌入。肠道和周围脂肪组织在解剖上密切相关，暗示着直接的相互免疫关系，而脂肪细胞配备了一整套先天免疫传感器，可对入侵的刺激作出反应。结果，脂肪细胞及其祖细胞经历深刻的免疫表型变化，导致脂肪组织重塑并最终形成 creeping fat。事实上，creeping fat 是一个具有免疫活性的器官，可合成各种促炎和抗炎细胞因子、促纤维化介质和脂肪因子，作为旁分泌/自分泌信号，调节免疫反应。因此，creeping fat 似乎参与了炎症信号转导，这也解释了为什么它与克罗恩病的更高严重程度或复杂表型有关。有趣的是，越来越多的证据表明 creeping fat 具有作为第二种屏障的替代免疫调节功能，以牺牲不断增殖的促纤维化环境为代价来防止异常的全身性炎症反应。需要进一步的研究来阐明这种改性脂肪组织在克罗恩病病程中如何发挥其拮抗作用。
