Historical rise of cancer and dietary linoleic acid: Mechanisms and therapeutic strategies

Figure 3 Proposed oxidative cascade linking excess linoleic acid to mitochondrial dysfunction and tumor promotion: Oxidation of membrane-bound linoleic acid yields 4 hydroxynonenal and related oxylipins, which impair mitochondrial respiration, elevate reactive oxygen species, and activate nuclear factor kappa-light-chain-enhancer of activated B cells-dependent inflammatory circuits; concurrent gut dysbiosis amplifies systemic cytokine tone, together fostering DNA damage and tumor promotion. Quantitative insets reflect representative preclinical data. GLUT-1: Glucose transporter 1; VEGF: Vascular endothelial growth factor; HIF-1α: Hypoxia-inducible factor-1α; ETC: Electron transport chain; SDH: Succinate dehydrogenase; LA: Linoleic acid.