Lipid metabolism in homeostasis and disease

Abstract Lipid metabolism is essential for maintaining cellular homeostasis, and its dysregulation is linked to various diseases, including cancer, cardiovascular disease, and diabetes. Immune cells, such as macrophages, T cells, B cells, and neutrophils, rely on lipid metabolism for their function, which impacts both innate and adaptive immune responses. Understanding how lipid metabolism influences immune cells is crucial, as it can reveal new therapeutic opportunities for immune-mediated diseases. In this review, we provide a retrospective summary of the research history and milestone events in lipid metabolism research and highlight the importance of lipid metabolism in immune cells. In addition to discussing the various lipid functions, transport, and signaling pathways involved in lipid metabolism, we mainly explore the regulation of immune cell behavior by lipid metabolism, focusing on the roles of lipid metabolites in immune cell proliferation, differentiation, and activation. We further highlight multilevel regulatory mechanisms, including genetic, epigenetic, posttranscriptional, and posttranslational regulation, and their impact on immune cell function. Additionally, we discuss the role of lipid metabolism in diseases such as autoimmune diseases, cancer, neurodegenerative diseases, cardiovascular diseases, aging, and metabolic disorders. Finally, we summarize therapeutic strategies targeting lipid metabolism, the progress of global clinical trials, and future research directions, including lipid-derived biomarkers and innovative therapeutic approaches.