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

白色脂肪组织 脂肪细胞 内科学 内分泌学 褐变 脂肪组织 生物 医学 生物化学
作者
Lugen Zuo,Zhijun Geng,Xue Song,Jing Wang,Yueyue Wang,Qian Zhang,Sitang Ge,Lian Wang,Guangyong Liu,Lele Zhang,Mengyu Xu,Yajing Zhao,Li Shen,Yuanyuan Ge,Rong Wu,Jianguo Hu
出处
期刊:Journal of Crohn's and Colitis [Oxford University Press]
卷期号:17 (8): 1179-1192 被引量:4
标识
DOI:10.1093/ecco-jcc/jjad046
摘要

Abstract 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 well as colitis in TNBS-treated mice in vivo. The anti-inflammatory activity of beige adipocytes was at least partially related to STAT6 signalling activation via the autocrine and paracrine effects of IL-4. Conclusion White adipocyte browning is a newly identified pathological change in htMAT of CD patients and a possible therapeutic target.
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