Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including ‘EOCRC’, ‘obesity’, ‘obesity-related hormones’, ‘itaconate’, ‘adiponectin’, ‘leptin’, ‘M2a macrophage’, and ‘microbiome’. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.
肥胖相关的代谢功能障碍会导致慢性促炎状态，并产生全身性影响，包括改变巨噬细胞代谢。肿瘤相关巨噬细胞通过产生衣康酸盐等代谢产物与癌症形成相关。衣康酸盐可下调过氧化物酶体增殖物激活受体γ这一肿瘤抑制因子，并在M2样巨噬细胞中上调抗炎细胞因子。同样，瘦素和脂联素也通过改变PI3K/AKT通路内的基因表达影响巨噬细胞因子表达，并促进结直肠癌进展。该通路影响细胞增殖、分化和肿瘤发生。本文综述了导致早发性结直肠癌发生发展的肥胖相关激素及炎症机制。通过检索PubMed和Cochrane数据库，使用“早发性结直肠癌”“肥胖”“肥胖相关激素”“衣康酸盐”“脂联素”“瘦素”“M2a巨噬细胞”“微生物组”等关键词，筛选出肥胖与早发性结直肠癌相关研究。基于促炎标志物促进早发性结直肠癌发展的理论，增加阿司匹林等化学预防药物的使用可能具有保护作用。阐明肥胖相关激素/细胞因子驱动的炎症效应与早发性结直肠癌的关联，可能有助于发现预防和治疗早发性结直肠癌的新靶点。
Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer
肿瘤(癌症)患者之家