Lipid metabolism: a molecular switch to control inflammation

Lipid metabolism is essential for cellular energy homeostasis, structural integrity, and signal transduction, and exerts a dual role in inflammation by acting as both an initiator and a regulator. This review comprehensively explores the molecular basis underlying the interactions among lipid metabolic pathways, lipid-derived mediators, and immune-inflammatory processes, while highlighting their profound significance in metabolic and chronic diseases. The core processes of lipid metabolism profoundly influence the initiation and resolution of inflammation through the regulation of oxidative stress, lipid mediators, and key signaling pathways. Furthermore, dysregulated lipid metabolism drives the formation of a chronic inflammatory microenvironment via inducing macrophage polarization, altering lipid droplet dynamics in immune cells, and disrupting adipokine secretion, thereby promoting the progression of metabolic diseases. In addition, this review summarizes intervention strategies targeting key lipid metabolic enzymes, signaling pathways, and epigenetic modifications, demonstrating their remarkable potential in anti-inflammatory and metabolic regulatory applications. As a molecular switch governing inflammation, lipid metabolism establishes a bidirectional regulatory network with inflammation through five core processes, namely lipid uptake and transport, lipogenesis, cholesterol metabolism, fatty acid β-oxidation, and lipolysis. Finally, this review emphasizes the pivotal role of technologies such as lipidomics and systems biology in deciphering the lipid-inflammation interplay, providing detailed insights for targeted anti-inflammatory interventions. Future research should prioritize multidisciplinary collaborations, focus on organ-specific regulatory targets, develop precision therapies, and advance dual-target combination therapies for metabolism and immunity. Moreover, multi-omics technologies should be leveraged to construct disease prediction models for individualized interventions, ultimately driving innovations in therapeutic strategies for chronic inflammation-driven diseases (see Fig. 1).