Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
J Crohns Colitis. 2023 Aug 21;17(8):1179-1192. doi: 10.1093/ecco-jcc/jjad046.
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.
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.
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.
White adipocyte browning is a newly identified pathological change in htMAT of CD patients and a possible therapeutic target.
肥大肠系膜脂肪组织[htMAT]是克罗恩病[CD]的一个独特标志，它通过功能失调的白色脂肪细胞炎症脂肪因子分泌影响肠炎。白色脂肪细胞可以通过白色脂肪细胞棕色化变成米色脂肪细胞，米色脂肪细胞的特征是活跃的脂质消耗和有利的内分泌功能。我们的研究旨在确定 htMAT 是否发生白色脂肪细胞棕色化及其在 CD 中的作用。
检查了来自 CD 患者和对照者的 MAT 样本中的白色脂肪细胞棕色化。对人 MAT 外植体和原代肠系膜脂肪细胞进行了体外培养实验。使用 2,4,6-三硝基苯磺酸溶液[TNBS]诱导的结肠炎小鼠进行了体内研究。使用β3-肾上腺素能受体激动剂[CL316,243]诱导白色脂肪细胞棕色化，并分析了 IL-4/STAT6 信号通路，以探讨米色脂肪细胞抗炎活性的机制。
在 CD 患者的 htMAT 中观察到白色脂肪细胞棕色化，表现为具有脂质耗竭活性和抗炎内分泌特征的解偶联蛋白 1[UCP1]阳性多形[米色]脂肪细胞。来自 CD 患者和对照者的人 MAT 和原代肠系膜脂肪细胞都可以被诱导发生棕色化，这增加了它们在体外的脂质耗竭和抗炎活性。诱导 MAT 棕色化改善了 TNBS 处理小鼠体内肠系膜肥大和炎症以及结肠炎。米色脂肪细胞的抗炎活性至少部分与 STAT6 信号通路的激活有关，通过 IL-4 的自分泌和旁分泌作用。
白色脂肪细胞棕色化是 CD 患者 htMAT 中一种新发现的病理变化，可能是一种治疗靶点。
