Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis

Objective: The elevation of the levels of l-carnitine and its fatty acid esters, acylcarnitines, in tissue or plasma has been linked to the development of atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and transport, methyl-γ-butyrobetaine (methyl-GBB), was discovered. In this study, we evaluated the effects of γ-butyrobetaine (GBB), l-carnitine and methyl-GBB administration on the progression of atherosclerosis. Methods: Apolipoprotein E knockout (apoE^-/-) mice were treated with methyl-GBB, l-carnitine or GBB for 4months. Following the treatment, the amount of atherosclerotic lesions, the number of immune cells in atherosclerotic lesions and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after treatment with methyl-GBB at the dose of 10mg/kg. Results: Treatment with methyl-GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10. mg/kg reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB treatment affected the development of atherosclerosis. Conclusions: Methyl-GBB administration significantly attenuated the development of atherosclerosis in apoE^-/-mice. Our results demonstrate that decreasing the acylcarnitine pools can attenuate the development of atherosclerosis.