1. Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis.
- Author
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Vilskersts R, Kuka J, Liepinsh E, Makrecka-Kuka M, Volska K, Makarova E, Sevostjanovs E, Cirule H, Grinberga S, and Dambrova M
- Subjects
- Animals, Aorta drug effects, Aorta metabolism, Apolipoproteins E metabolism, Betaine pharmacology, Carnitine metabolism, Carnitine pharmacology, Disease Progression, Female, Male, Mice, Atherosclerosis drug therapy, Atherosclerosis metabolism, Betaine analogs & derivatives, Carnitine analogs & derivatives
- Abstract
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 10mg/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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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