From Damage Signals to Immune Modulators: Oxidized Lipids in Immunometabolic Inflammation

Oxidized lipids, once viewed as byproducts of oxidative stress, are now recognized as critical mediators linking metabolism, redox imbalance, and immunity. Generated through enzymatic and non-enzymatic oxidation of polyunsaturated fatty acids, oxidized phospholipids, lipid aldehydes, and oxidized lipoproteins act as context-dependent signals regulating immune activation, resolution, and metabolic adaptation. In metabolic inflammation, these lipids engage scavenger and Toll-like receptors to influence macrophage polarization, dendritic-cell function, and T-cell differentiation. Their context and concentration determine whether oxidized lipids amplify inflammation or promote immune tolerance. Accumulation of these species connects oxidative stress to immune dysfunction, contributing to diseases such as atherosclerosis, obesity, diabetes, cancer, and autoimmunity. This review synthesizes mechanistic and disease-specific insights into how oxidized lipids shape innate and adaptive immune responses in metabolic and autoimmune inflammation. As advances in lipidomics and immunology converge, a deeper understanding of oxidized-lipid regulation and function will enable the development of targeted strategies to restore immune and metabolic balance in chronic inflammatory disease.