Mechanisms underlying obesity-malignancy connection: a systematic narrative review.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ayesha Sultana, Sobia Rana
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引用次数: 0

Abstract

The association between obesity and cancer risk carries substantial public health ramifications as obesity promotes cancer advancement via many cellular and molecular mechanisms. This study utilizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and narrative systematic review guidelines to evaluate 221 research articles selected from an initial collection of 1,288 publications sourced from multiple databases. Obesity-driven cancer risk is linked to hormonal imbalances including increased oestrogen levels that heighten the likelihood of breast and endometrial cancers, and insulin resistance that activates the insulin/ Insulin and Insulin-like Growth Factor 1 (IGF-1) pathway promoting colorectal cancer progression. Chronic low-grade inflammation, metabolic dysfunction, and hypoxia in expanding adipose tissue contribute to pancreatic, oesophageal, colorectal, renal, and liver malignancies. Recent research has identified novel mechanisms that drive obesity-induced cancer progression. The adipose tissue secretome, extracellular vesicle-mediated lipid and RNA transfer, ferroptosis resistance, and metabolic reprogramming via Cluster of Differentiation 36 (CD36), Fatty Acid Binding Protein 4 (FABP4), and Carnitine Palmitoyl transferase 1A (CPT1A) create a tumour-permissive microenvironment. Obesity-induced epigenetic memory sustains cancer risk even after weight loss through persistent histone modifications (Histone H3 Lysine 4 Trimethylation (H3K4me3), Histone H3 Lysine 27 Trimethylation (H3K27me3), DNA methylation, and RNA modifications, particularly through the Fat Mass and Obesity-Associated (FTO) gene. Additionally, organ and cell size expansion increase mutation susceptibility. Emerging pathways including the Von Hippel-Lindau (VHL)-Hypoxia-Inducible Factor (HIF) axis, PR Domain Zinc Finger Protein 16 (PRDM16)/Uncoupling Protein 1 (UCP1) inhibition, Signal Transducer and Activator of Transcription 3 (STAT3)-driven FABP4 upregulation, and Yes-Associated Protein (YAP)/Transcriptional Co-Activator with PDZ-Binding Motif (TAZ) signalling, further highlight obesity's role in oncogenesis. Future research should investigate weight-loss drugs' effects on cancer pathways, expand demographic diversity, and develop biomarkers for adiposity. Integrating Mendelian randomization, multi-omics, and artificial intelligence could reveal novel therapeutic targets. A comprehensive prevention strategy combining lifestyle interventions, pharmacological therapies, and biomarker-driven diagnostics is crucial to reducing obesity-related cancer burden and improving patient outcomes.

肥胖与恶性肿瘤联系的机制:一个系统的叙述综述。
肥胖与癌症风险之间的关联具有重大的公共卫生影响,因为肥胖通过许多细胞和分子机制促进癌症的进展。本研究采用系统评价和荟萃分析首选报告项目(PRISMA)和叙述性系统评价指南,从多个数据库的1,288份出版物的初始收集中选择221篇研究文章进行评估。肥胖导致的癌症风险与激素失衡有关,包括雌激素水平升高,增加患乳腺癌和子宫内膜癌的可能性,以及胰岛素抵抗,激活胰岛素/胰岛素和胰岛素样生长因子1 (IGF-1)通路,促进结直肠癌的进展。慢性低度炎症、代谢功能障碍和扩张脂肪组织缺氧可导致胰腺、食管、结肠、肾脏和肝脏恶性肿瘤。最近的研究已经确定了驱动肥胖引起的癌症进展的新机制。脂肪组织分泌组、细胞外囊泡介导的脂质和RNA转移、铁凋亡抵抗以及通过分化簇36 (CD36)、脂肪酸结合蛋白4 (FABP4)和肉毒碱棕榈酰转移酶1A (CPT1A)进行的代谢重编程创造了一个肿瘤允许的微环境。肥胖诱导的表观遗传记忆通过持续的组蛋白修饰(组蛋白H3赖氨酸4三甲基化(H3K4me3)、组蛋白H3赖氨酸27三甲基化(H3K27me3)、DNA甲基化和RNA修饰,特别是通过脂肪质量和肥胖相关(FTO)基因,即使在体重减轻后,也会维持癌症风险。此外,器官和细胞大小的扩大增加了突变的易感性。包括Von Hippel-Lindau (VHL)-缺氧诱导因子(HIF)轴、PR结构域锌指蛋白16 (PRDM16)/解偶联蛋白1 (UCP1)抑制、信号转导和转录激活因子3 (STAT3)驱动的FABP4上调以及细胞相关蛋白(YAP)/ pdz结合Motif转录共激活因子(TAZ)信号传导在内的新途径进一步强调了肥胖在肿瘤发生中的作用。未来的研究应该调查减肥药对癌症途径的影响,扩大人口统计学的多样性,并开发肥胖的生物标志物。整合孟德尔随机化、多组学和人工智能可以揭示新的治疗靶点。将生活方式干预、药物治疗和生物标志物驱动的诊断相结合的综合预防策略对于减少与肥胖相关的癌症负担和改善患者预后至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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