Effect of Fungal Metabolites Cytochalasans on Lipid Droplet Formation in Mouse Macrophages

Abstract

Effects of seven cytochalasans including cytochalasins B, D and E and novel phenochalasins A and B were tested on cytosolic lipid droplet formation and neutral lipid synthesis in mouse peritoneal macrophages. Phenochalasin A inhibited lipid droplet formation in a dose-dependent manner at least up to 20μM without any morphological changes in macrophages. Cytochalasins D and E also inhibited lipid droplet formation only in a narrow range of concentrations, around 1 and 0.1μM, respectively. At higher concentrations they gave morphological changes in macrophages. The other four cytochalasans only showed severe morphological changes in macrophages. Phenochalasin A and cytochalasins D and E inhibited cholesteryl ester (CE) synthesis specifically with IC₅₀ values of 0.61, 2.4 and 0.20μM, respectively, while the other cytochalasans inhibited both CE and triacylglycerol syntheses. Thus, among the cytochalasans tested, phenochalasin A showed very specific inhibition of CE synthesis and gave the lowest morphological changes in macrophages, resulting in the best inhibitor of lipid droplet formation in macrophages.