过度肥胖会导致结肠癌（CC）的发生。白细胞介素 (IL)-1β 是一种促炎细胞因子，与肥胖相关的慢性炎症和致瘤过程相关。我们在此旨在研究肥胖和CC如何影响IL1B的表达，并确定IL-1β在肥胖和CC的背景下对代谢炎症和肠道屏障功能的调节的影响。来自 71 名志愿者的样本被用于病例对照研究和饮食诱导肥胖 (DIO) 大鼠模型。此外，还使用减肥手术来确定减肥对 Il1b 肠道基因表达水平的影响。为了评估 IL-1β 和肥胖对 CC 的影响，我们用 IL-1β 和来自肥胖患者的脂肪细胞条件培养基 (ACM) 处理腺癌细胞系 HT-29。我们发现，肥胖 (P<0.05) 和 CC (P<0.01) 上调了 CC 患者内脏脂肪组织和结肠中 IL1B 的转录水平 (P<0.01)。通过袖状胃切除术或热量限制实现体重减轻后，DIO 大鼠回肠和结肠中 Il1b 的表达增加减少（P<0.05）。对 HT-29 细胞进行 ACM 处理后，IL1B 和 CCL2 的转录上调（P<0.05），同时降低抗炎 ADIPOQ 和 MUC2 基因的表达（P<0.05）。此外，IL-1β上调（P<0.01）CCL2和TNF的表达，同时下调（P<0.01）HT-29细胞中IL4、ADIPOQ和TJP1的转录水平。我们提供了 IL-1β 通过直接促进炎症在肥胖相关 CC 中发挥重要作用的证据。© 2024。作者。

Excess adiposity contributes to the development of colon carcinoma (CC). Interleukin (IL)-1β is a pro-inflammatory cytokine relevant in obesity-associated chronic inflammation and tumorigenic processes. We herein aimed to study how obesity and CC affects the expression of IL1B, and to determine the impact of IL-1β on the regulation of metabolic inflammation and gut barrier function in the context of obesity and CC. Samples from 71 volunteers were used in a case-control study and a rat model of diet-induced obesity (DIO). Furthermore, bariatric surgery was used to determine the effect of weight loss on the intestinal gene expression levels of Il1b. To evaluate the effect of IL-1β and obesity in CC, we treated the adenocarcinoma cell line HT-29 with IL-1β and the adipocyte-conditioned medium (ACM) from patients with obesity. We showed that obesity (P < 0.05) and CC (P < 0.01) upregulated the transcript levels of IL1B in visceral adipose tissue as well as in the colon from patients with CC (P < 0.01). The increased expression of Il1b in the ileum and colon in DIO rats decreased after weight loss achieved by either sleeve gastrectomy or caloric restriction (both P < 0.05). ACM treatment on HT-29 cells upregulated (P < 0.05) the transcripts of IL1B and CCL2, while reducing (P < 0.05) the expression of the anti-inflammatory ADIPOQ and MUC2 genes. Additionally, IL-1β upregulated (P < 0.01) the expression of CCL2 and TNF whilst downregulating (P < 0.01) the transcript levels of IL4, ADIPOQ and TJP1 in HT-29 cells. We provide evidence of the important role of IL-1β in obesity-associated CC by directly promoting inflammation.© 2024. The Author(s).