Volume 28, Issue S1 249.6
Nutrition
Free Access

TMAO an L-carnitine metabolite does not affect foam cell formation or cholesterol efflux in J774 mouse macrophage (249.6)

Aouatef Bellamine

Aouatef Bellamine

Toxicology Lonza Allendale, NJ, United States

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Denise Drazul-Schrader

Denise Drazul-Schrader

Research Vascular Strategies Plymouth, Meeting, PA, United States

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Heidi Collins

Heidi Collins

Research Vascular Strategies Plymouth, Meeting, PA, United States

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Kevin Owen

Kevin Owen

Nutrition Lonza Allendale, NJ, United States

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Nick Skoulis

Nick Skoulis

Toxicology Lonza Allendale, NJ, United States

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Steve Adelman

Steve Adelman

Research Vascular Strategies Plymouth, Meeting, PA, United States

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Abstract

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.