Foamy macrophages, characterized by prominent lipid droplets (LDs), are implicated in various diseases. Toll-like receptor agonists stimulate triacylglycerol (TG)-rich LD development in macrophages. This study investigates the underlying mechanisms and significance of this process. Results reveal that LD development stems from metabolic commitment to TG synthesis alongside reduced fatty acid oxidation. TG synthesis is crucial for optimal inflammatory macrophage activation; its inhibition markedly reduces inflammatory mediators (IL-1β, IL-6, PGE₂) and phagocytic capacity. The impaired PGE₂ production is key, as exogenous PGE₂ reverses the anti-inflammatory effects of TG synthesis inhibition. These findings highlight the central role of LDs in inflammatory macrophage activation.

Angela Castoldi, Lauar B. Monteiro, Nikki van Teijlingen Bakker, David E. Sanin, Nisha Rana, Mauro Corrado, Alanna M. Cameron, Fabian Hässler, Mai Matsushita, George Caputa, Ramon I. Klein Geltink, Jörg Büscher, Joy Edwards-Hicks, Erika L. Pearce, Edward J. Pearce