Hu Jun-Jie, Zhang Qi-Yue, Yang Zhi-Chun
Hunan University of Traditional Chinese Medicine, Changsha, 410078, China.
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
Eur J Med Res. 2025 May 26;30(1):419. doi: 10.1186/s40001-025-02659-4.
This study reviews the mechanisms by which obesity affects the development and progression of breast cancer (BC). The association between obesity and BC is mainly due to three aspects: disruption of glycolipid metabolism, abnormal cell function and imbalance of adipokine levels. The dysregulation of glycolipid metabolism caused by obesity, including the accumulation of cholesterol and fatty acids and the reprogramming of glucose metabolism, promotes the growth and invasion of tumour cells. Obesity triggers multiple cellular abnormalities, particularly in lipid-associated macrophages and cancer-associated adipocytes, which promote tumour progression and immunosuppression by secreting inflammatory factors and various fatty acids into the tumour microenvironment. Obesity leads to an imbalance in the expression of several adipokines. Leptin upregulation is closely associated with BC metastasis and resistance to endocrine therapy, while reduced adiponectin levels attenuate the protective effect. At the same time, chronic inflammation and insulin resistance not only further increase the risk of BC, but also exacerbate tumour resistance. In terms of treatment, weight-loss drugs and metformin can improve the efficacy of obesity-related BC treatment to some extent. Intervention strategies targeting adipose tissue remodelling, lipid metabolism and leptin regulation also show potential clinical value, but more research is needed to clarify their safety and efficacy. This review provides systematic ideas and references for research into the mechanisms and clinical management of obesity-related BC.
本研究综述了肥胖影响乳腺癌(BC)发生发展的机制。肥胖与BC之间的关联主要体现在三个方面:糖脂代谢紊乱、细胞功能异常和脂肪因子水平失衡。肥胖引起的糖脂代谢失调,包括胆固醇和脂肪酸的积累以及葡萄糖代谢重编程,促进肿瘤细胞的生长和侵袭。肥胖引发多种细胞异常,尤其是在脂质相关巨噬细胞和癌症相关脂肪细胞中,这些细胞通过向肿瘤微环境中分泌炎性因子和各种脂肪酸促进肿瘤进展和免疫抑制。肥胖导致多种脂肪因子表达失衡。瘦素上调与BC转移及内分泌治疗耐药密切相关,而脂联素水平降低则削弱了其保护作用。同时,慢性炎症和胰岛素抵抗不仅进一步增加BC风险,还加剧肿瘤耐药。在治疗方面,减肥药物和二甲双胍可在一定程度上提高肥胖相关BC的治疗效果。针对脂肪组织重塑、脂质代谢和瘦素调节的干预策略也显示出潜在临床价值,但需要更多研究来阐明其安全性和有效性。本综述为肥胖相关BC的机制研究和临床管理提供了系统思路和参考。