TMAO an L-carnitine metabolite does not affect foam cell formation or cholesterol efflux in J774 mouse macrophage (249.6)
Trimethylamine N-oxide (TMAO) is a common metabolite of the L-carnitine, recently linked to atherosclerosis initiation and progression in mice. TMAO was associated with a modest increase in the RNA levels of known cholesterol transporters and suggested to drive changes in the reverse cholesterol transport (RCT) pathway. To assess the direct effect of TMAO on two components of atherosclerosis: foam cell formation and cholesterol efflux, J774 mouse macrophages were exposed to increasing concentration of TMAO (0, 1, 3, 10, 30 and 100 μM) in presence of 12 and 50 μg/ml acetylated LDL (acLDL) for 24 hours and cholesterol content and cholesterol efflux were measured. No changes in total, free or esterified cholesterol mass in response to acLDL were observed at any TMAO concentration. Furthermore, when apo-AI was used as cholesterol acceptor, TMAO did not affect ABCA1 cholesterol-mediated efflux. When using HDL3, an acceptor for cholesterol efflux mediated by SR-BI, ABCG1 or passive diffusion, TMAO did not affect cholesterol efflux. Together, these results suggest that neither cholesterol efflux via ABCA1, ABCG1 or SR-BI nor cholesterol loading were affected by TMAO up to 100 μM (about 10-fold higher than the Cmax in humans). In conclusion, TMAO up to 100 μM showed no effect on foam cell development or inhibition of cholesterol efflux, major pathways in atherosclerotic disease development.