The Effect of Different l-Carnitine Administration Routes on the Development of Atherosclerosis in ApoE Knockout Mice.

Abstract

l-Carnitine (LC) is abundant in red meat and is widely added to health supplements and food. This study focuses on the adverse effects of oral supplementation of 1.3% LC in ApoE-/- mice and whether the parenteral administration of LC (subcutaneously, sub) has any impact on the development of atherosclerosis. Mice are randomly divided into three groups (n=15). All mice are fed a high-fat diet (HFD). The number of Ly6Chi monocytes; degree of atherosclerosis; plasma LC, γ-butyrobetaine (γBB), and trimethylamine-N-oxide (TMAO) levels; and microbial community composition are analyzed. Compared with the HFD and HFD±LC (sub) groups, the number of Ly6Chi monocytes, atherosclerotic plaque area, and plasma γBB and TMAO levels are increased in the HFD±LC (oral) group (p<0.001). Plasma LC levels in the HFD±LC (sub) group are higher than those in other groups. The levels of γBB, TMAO, and Ly6Chi monocytes are positively correlated with atherosclerotic plaque area (p<0.01), and TMAO is positively correlated with Bacteroidetes and negatively correlated with Firmicutes at the phylum level. In contrast with oral LC administration, subcutaneous LC administration, which bypasses its conversion to TMAO in the liver, does not have a detrimental effect on the development of atherosclerosis in male ApoE-/- mice. Taking LC parenterally may be preferable among patients who require LC supplementation.