Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, China.
Nat Commun. 2023 Sep 20;14(1):5830. doi: 10.1038/s41467-023-41418-z.
Creeping fat is a typical feature of Crohn's disease. It refers to the expansion of mesenteric adipose tissue around inflamed and fibrotic intestines and is associated with stricture formation and intestinal obstruction. In this study, we characterize creeping fat as pro-adipogenic and pro-fibrotic. Lipidomics analysis of Crohn's disease patients (sixteen males, six females) and healthy controls (five males, ten females) reveals abnormal lipid metabolism in creeping fat. Through scRNA-seq analysis on mesenteric adipose tissue from patients (five males, one female) and healthy controls (two females), we identify a CCL2DPP4 subset of mesenchymal stem cells that expands in creeping fat and expedites adipogenic differentiation into dystrophic adipocytes in response to CCL20CD14 monocytes and IL-6, leading to the formation of creeping fat. Ex vivo experiments (tissues from five males, one female) confirm that both CCL20CD14 monocytes and IL-6 activate DPP4 mesenchymal stem cells towards a pro-adipogenic phenotype. This study provides a comprehensive investigation of creeping fat formation and offers a conceptual framework for discovering therapeutic targets for treatment of Crohn's disease.
creeping 脂肪是克罗恩病的典型特征。它指的是围绕炎症和纤维化肠道扩张的肠系膜脂肪组织，与狭窄形成和肠梗阻有关。在这项研究中，我们将 creeping 脂肪描述为促脂肪生成和促纤维化的。对克罗恩病患者（16 名男性，6 名女性）和健康对照者（5 名男性，10 名女性）的脂质组学分析显示 creeping 脂肪存在异常的脂质代谢。通过对患者（5 名男性，1 名女性）和健康对照者（2 名女性）肠系膜脂肪组织的 scRNA-seq 分析，我们鉴定出在 creeping 脂肪中扩张的 CCL2DPP4 亚群间充质干细胞，它响应 CCL20CD14 单核细胞和 IL-6 加速向脂肪生成分化为营养不良脂肪细胞，导致 creeping 脂肪的形成。离体实验（来自 5 名男性，1 名女性的组织）证实，CCL20CD14 单核细胞和 IL-6 均可激活 DPP4 间充质干细胞向促脂肪生成表型转化。这项研究全面调查了 creeping 脂肪的形成，并为发现治疗克罗恩病的治疗靶点提供了一个概念框架。
