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

Abstract

Scope: 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.

Methods and results: Mice are randomly divided into three groups (n = 15). All mice are fed a high-fat diet (HFD). The number of Ly6C^hi 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 Ly6C^hi 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 Ly6C^hi 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.

Conclusion: 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.

Keywords: Ly6Chi monocyte subset; atherosclerosis; l-carnitine; microbiota; trimethylamine-N-oxide (TMAO).