Lipid metabolic alterations in cancer: Common pathophysiology with cardiovascular disease

Obesity-induced chronic inflammation and lipid metabolic imbalance form a pivotal nexus linking cardiovascular disease and cancer. Dysfunctional adipose tissue establishes a pro-inflammatory environment through hypoxia-driven macrophage polarization, oxidative stress, aberrant lipid signaling, and endocrine crosstalk, mechanisms that collectively foster atherogenesis and tumor promotion. Yet, a comprehensive integration of metabolic and immunological dynamics at the molecular level remains elusive. In this review, we synthesize emerging evidence that metabolic stressors, particularly excessive intake of oxidized and omega-6-enriched lipids, activate NF-κB and NLRP3-dependent inflammatory pathways in macrophages, thereby fostering a pro-tumorigenic and pro-atherogenic microenvironment. We underscore the emerging role of microRNAs as functional mediators connecting lipid metabolism, inflammation, and cellular plasticity across atherosclerotic and neoplastic tissues. These non-coding RNAs modulate key signaling pathways, including the critical PI3K/Akt, NFκB, and TGFβ axes, thereby promoting macrophage phenotype shifts, endothelial dysfunction, aberrant proliferation, and immune evasion. Importantly, interventions aimed at restoring lipid homeostasis, including Mediterranean-style diets, caloric restriction, and regular physical activity, act as important regulators of systemic and tissue-specific inflammation. Nutritional interventions increase monounsaturated and omega-3 fatty acid content and limit oxidized lipid exposure. We propose that combining metabolic modulation with RNA-based therapies, such as miRNA mimics or inhibitors delivered through nanoparticles or pH-responsive peptide systems, may offer synergistic avenues for controlling metabolic inflammation in both cancer and cardiovascular disease. Future research should focus on the targeted and context-dependent regulation of non-coding RNA networks within immuno-metabolic circuits, advancing precision medicine in cardio-oncology.