肥胖中IL-1β在脂肪组织中的表达升高通过促进炎症影响结肠癌的发展
Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation
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影响因子:4.3
分区:生物学3区 / 生化与分子生物学3区 生理学3区
发表日期:2025 May
作者:
Gabriela Neira, Javier Gómez-Ambrosi, Javier A Cienfuegos, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, María A Burrell, Jorge Baixauli, Amaia Mentxaka, Marcos Casado, Camilo Silva, Javier Escalada, Gema Frühbeck, Victoria Catalán
DOI:
10.1007/s13105-024-01048-5
摘要
过量脂肪积聚促进结肠癌（CC）的发生。白细胞介素（IL）-1β是一种相关于肥胖相关慢性炎症和肿瘤发生过程的促炎细胞因子。本研究旨在探讨肥胖和CC如何影响IL1B的表达，以及IL-1β在调节代谢性炎症和肠道屏障功能中的作用。我们利用71名志愿者的样本进行病例对照研究，并采用饮食诱导肥胖（DIO）大鼠模型。此外，采用减重手术评估减重对肠道中Il1b基因表达的影响。我们还用IL-1β和肥胖患者提供的脂肪细胞条件培养基（ACM）处理结肠腺癌细胞系HT-29，研究其作用机制。结果显示，肥胖（P<0.05）和CC（P<0.01）均上调了内脏脂肪组织以及CC患者结肠中的IL1B转录水平。DIO大鼠的Il1b在回肠和结肠的表达在减重（袖状胃切除术或热量限制）后均降低（均P<0.05）。ACM处理HT-29细胞，显著上调（P<0.05）IL1B和CCL2的转录，同时降低（P<0.05）抗炎基因ADIPOQ和MUC2的表达。此外，IL-1β还上调（P<0.01）CCL2和TNF的表达，同时下调（P<0.01）IL4、ADIPOQ和TJP1在HT-29细胞中的转录水平。我们的研究提供了IL-1β在肥胖相关结肠癌中通过直接促进炎症发挥重要作用的证据。
Abstract
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.