Lipid-associated macrophages and metabolic inflammatory diseases

Lipid metabolism disorders have been identified in various chronic diseases that are also closely linked with immune cells and inflammatory microenvironment. As pivotal innate immune cells, macrophages exhibit remarkable heterogeneity. Lipid-associated macrophages (LAMs) have emerged as a distinct subtype, characterized by high expression of lipid metabolism-related genes and abundant intracellular lipid droplets (LDs). Accumulating evidence suggests LAMs at the crossroads of lipid dysregulation and inflammation during the development of various diseases. This review focuses on LAMs in four pathological contexts: the adipose tissue in obesity, the liver in lipid metabolism disorders, atherosclerotic cardiovascular diseases, and the brain in neurodegenerative diseases. The features of LAMs, including specific markers, cellular origins, tissue-specific localization, and their regulatory roles in lipid metabolism, inflammation as well as tissue injury or repair within these pathological microenvironments, are discussed. Additionally, multiple LAM-related molecular targets and relevant clinical trials across different disease conditions are summarized, providing insights for future research and clinical translation in chronic inflammatory diseases.