Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation

Figures

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  Fig. 1. (A) Gene expression levels of IL1B visceral adipose tissue (VAT) and (B) circulating levels of IL-1β from normal weight (NW) volunteers and patients with obesity (OB) classified according to the presence or absence of colon cancer (CC) [NW-nonCC: n = 11; OB-non CC: n = 34; NW-CC: n = 13; OB-CC: n = 13]. (C) IL1B mRNA levels in the colon from patients with and without CC [nonCC: n = 7; CC: n = 11]. Differences between groups were analyzed by two-way ANCOVA and by two-tailed unpaired Student’s t-tests. Bars represent the mean ± SEM. **P < 0.01

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  Fig. 2. Gene expression levels of Il1b in the duodenum, jejunum, ileum and colon of rats under a (A) normal diet (ND, n = 10) and high fat diet (HFD, n = 10) as well as (B) after bariatric surgery [Sham, n = 6; sleeve gastrectomy (SG), n = 6; pair-fed (PF), n = 6]. All bar graph values are expressed as the mean ± SEM. Differences between groups were analyzed by an unpaired Student t-test, and a one-way ANOVA followed by Tukey’s post hoc tests. *P < 0.05 and **P < 0.01. SG, sleeve gastrectomy; PF, pair-fed

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  Fig. 3. Effect of adipocyte-conditioned media (ACM) on the gene expression levels of IL1B as well as on inflammation- and intestinal integrity-associated markers. Bar graphs show the effect of ACM (20 and 40%) from individuals with obesity incubated for 24 h on the transcript levels of (A) interleukin (IL)-1B, IL18, monocyte chemoattractant protein-1 (CCL2), tumor necrosis factor-α (TNF) and nucleotide-binding oligomerization domain, leucine rich repeat and pyrin 3 (NLRP3) and (B) adiponectin (ADIPOQ), IL4, mucin-2 (MUC2), tight junction protein 1 (TJP1) and fibronectin type III domain containing protein 4 (FNDC4). Values are the mean ± SEM (n = 5–6 per group). Differences between groups were analyzed by one-way ANOVA followed by Dunnett’s post hoc tests. *P < 0.05 and **P < 0.01

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  Fig. 4. Effect of IL-1β treatment on the expression levels of (A) pro- and (B) anti-inflammatory markers in HT-29 cells. Values are the mean ± SEM (n = 5–6 per group). Differences between groups were analyzed by one-way ANOVA followed by Dunnett’s post hoc tests. **P < 0.01. ADIPOQ, adiponectin; CCL2, monocyte chemoattractant protein-1; FNDC4, fibronectin type III domain containing protein 4; IL, interleukin; MUC, mucin-2; NLRP3, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin; TJP1, tight junction protein 1; TNF, tumor necrosis factor-α

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  Fig. 5. IL-1β is upregulated in VAT from patients with OB and CC and in the colon tissue from patients with CC. Weight loss achieved by either sleeve gastrectomy or caloric restriction downregulated the expression of Il1b in an animal model. In turn, IL-1β contributes to the inflammatory milieu in obesity-associated CC by upregulating pro-inflammatory factors such as TNF and CCL2 and downregulating the anti-inflammatory factors as IL4, ADIPOQ, FNDC4 and TJP1, mainly involved in the regulation of the intestinal barrier integrity. The treatment of the adenocarcinoma HT-29 cell line with the ACM obtained from patients with obesity upregulated the expression of pro-inflammatory IL1B, NLRP3, TNF and CCL2 while downregulating anti-inflammatory ADIPOQ and MUC2. ACM, adipocyte conditioned media; ADIPOQ, adiponectin; CCL2, monocyte chemoattractant protein-1; FNDC4, fibronectin type III domain containing protein 4; IL, interleukin; MUC, mucin-2; NLRP3, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin; TJP1, tight junction protein 1; TNF, tumor necrosis factor-α