L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP.

摘要: Abstract Objective Dietary l-carnitine can be metabolized by intestinal microbiota to trimethylamine, which is absorbed the gut and further oxidized trimethylamine N-oxide (TMAO) in liver. TMAO plasma levels have been associated with atherosclerosis development ApoE −/− mice. To better understand mechanisms behind this association, we conducted in vitro in vivo studies looking at effect of on different steps atherosclerotic disease progression. Methods J774 mouse macrophage cells were used evaluate foam cell formation. Male mice transfected human cholesteryl ester transfer protein (hCETP) fed and/or methimazole, a flavin monooxygenase 3 (FMO3) inhibitor that prevents formation TMAO. Following 12 week treatment, levels, aortic lesion development, lipid profiles determined. Results concentrations up 10-fold Cmax reported humans did not affect In expressing hCETP, high doses resulted significant increase levels. Surprisingly, independently from treatment group, inversely correlated size both root thoracic aorta. High found significantly correlate smaller area. Plasma lipoprotein change nor suggesting observed effects area independent changes. Conclusion These findings suggest slows model may protective against humans.