Solsona-Vilarrasa Estel, Vousden Karen H
The Francis Crick Institute, London, UK.
FEBS J. 2025 May;292(9):2189-2207. doi: 10.1111/febs.17312. Epub 2024 Nov 4.
White adipose tissue (WAT) is crucial for whole-body energy homeostasis and plays an important role in metabolic and hormonal regulation. While healthy WAT undergoes controlled expansion and contraction to meet the body's requirements, dysfunctional WAT in conditions like obesity is characterized by excessive tissue expansion, alterations in lipid homeostasis, inflammation, hypoxia, and fibrosis. Obesity is strongly associated with an increased risk of numerous cancers, with obesity-induced WAT dysfunction influencing cancer development through various mechanisms involving both systemic and local interactions between adipose tissue and tumors. Unhealthy obese WAT affects circulating levels of free fatty acids and factors like leptin, adiponectin, and insulin, altering systemic lipid metabolism and inducing inflammation that supports tumor growth. Similar mechanisms are observed locally in an adipose-rich tumor microenvironment (TME), where WAT cells can also trigger extracellular matrix remodeling, thereby enhancing the TME's ability to promote tumor growth. Moreover, tumors reciprocally interact with WAT, creating a bidirectional communication that further enhances tumorigenesis. This review focuses on the complex interplay between obesity, WAT dysfunction, and primary tumor growth, highlighting potential targets for therapeutic intervention.
白色脂肪组织（WAT）对于全身能量稳态至关重要，并且在代谢和激素调节中发挥重要作用。健康的白色脂肪组织会经历可控的扩张和收缩以满足身体需求，而在肥胖等情况下功能失调的白色脂肪组织的特征是组织过度扩张、脂质稳态改变、炎症、缺氧和纤维化。肥胖与多种癌症风险增加密切相关，肥胖诱导的白色脂肪组织功能障碍通过涉及脂肪组织与肿瘤之间全身和局部相互作用的各种机制影响癌症发展。不健康的肥胖白色脂肪组织会影响游离脂肪酸以及瘦素、脂联素和胰岛素等因子的循环水平，改变全身脂质代谢并引发支持肿瘤生长的炎症。在富含脂肪的肿瘤微环境（TME）中也观察到类似机制，其中白色脂肪组织细胞还可触发细胞外基质重塑，从而增强肿瘤微环境促进肿瘤生长的能力。此外，肿瘤与白色脂肪组织相互作用，形成双向通讯，进一步增强肿瘤发生。本综述重点关注肥胖、白色脂肪组织功能障碍与原发性肿瘤生长之间的复杂相互作用，突出治疗干预的潜在靶点。
