Browning of Mesenteric White Adipose Tissue in Crohn’s Disease: A New Pathological Change and Therapeutic Target

作者：Lugen Zuo, Zhijun Geng, Xue Song, Jing Li, Yueyue Wang, Xiaofeng Zhang, Sitang Ge, Lian Wang, Guangyong Liu, Lele Zhang, Mengyu Xu, Yajing Zhao, Li Shen, Yuanyuan Ge, Rong Wu, Jianguo Hu · 发表于：Journal of Crohn s and Colitis · 年份：2023 · DOI：10.1093/ecco-jcc/jjad046 · 被引用次数：16 · 研究领域：Inflammatory Bowel Disease、Adipose Tissue and Metabolism、Adipokines, Inflammation, and Metabolic Diseases

BACKROUND: Hypertrophic mesenteric adipose tissue [htMAT] is a distinctive hallmark of Crohn's disease [CD], and it affects enteritis via inflammatory adipokine secretion by dysfunctional white adipocytes. White adipocytes can become beige adipocytes, which are characterized by active lipid consumption and favourable endocrine function, via white adipocyte browning. Our study aimed to determine whether white adipocyte browning occurs in htMAT and its role in CD. METHODS: White adipocyte browning was examined in MAT samples from CD patients and controls. Human MAT explants and primary mesenteric adipocytes were cultured for in vitro experiments. Mice with 2,4,6-trinitrobenzenesulphonic acid solution [TNBS]-induced colitis were used for in vivo studies. A β3-adrenergic receptor agonist [CL316,243] was used to induce white adipocyte browning, and IL-4/STAT6 signalling was analysed to explore the mechanism underlying the anti-inflammatory activity of beige adipocytes. RESULTS: White adipocyte browning was observed in htMAT from CD patients, as shown by the appearance of uncoupling protein 1 [UCP1]-positive multilocular [beige] adipocytes with lipid-depleting activity and anti-inflammatory endocrine profiles. Both human MAT and primary mesenteric adipocytes from CD patients and controls could be induced to undergo browning, which increased their lipid-depleting and anti-inflammatory activities in vitro. Inducing MAT browning ameliorated mesenteric hypertrophy and inflammation as w...