Study summary · research use only
Acetyl-L-carnitine ameliorates atherosclerosis in LDLR(-/-) mice by modulating cholesterol metabolism through SREBP2-dependent cholesterol biosynthesis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study combined human plasma data from 494 individuals with hyperlipidemia and a murine model (LDLR-/- mice) to examine acetyl-L-carnitine (ALC) and cholesterol metabolism. Plasma ALC concentrations were negatively correlated with total cholesterol (TC; r = -0.43, p < 0.0001) and LDL-C (r = -0.53, p < 0.0001). In mice, dietary ALC reduced plasma TC and LDL-C, downregulated SREBP2 and HMG-CoA reductase expression, upregulated LDL receptor expression, and reduced atherosclerotic plaque formation in LDLR-/- mice. The authors describe ALC as acting through suppression of SREBP2-mediated cholesterol synthesis and suggest it as a potential subject for further study as an ASCVD therapeutic target.
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality globally. Hypercholesterolemia accelerates atherosclerotic development and is an independent modifiable risk factor for ASCVD. Reducing cholesterol levels is effective in preventing ASCVD. Acetyl-L-carnitine (ALC) is an endogenous molecule that plays a primary role in energy metabolism; however, its effect on cholesterol metabolism remains unclear. We collected plasma samples and clinical data from 494 individuals with hyperlipidemia. Targeted metabolomics were used to measure plasma ALC levels and explore the association of ALC with clinical cholesterol levels. Additionally, we explored the effects of ALC in cholesterol levels and cholesterol metabolism in a murine hypercholesterolemia model. An LDLR-/- mouse-based atherosclerotic model was established to investigate the roles of ALC on atherosclerotic progression. Plasma ALC concentrations were significantly negatively correlated with plasma total cholesterol (TC) levels (r = -0.43, p < 0.0001) and low-density lipoprotein cholesterol (LDL-C; r = -0.53, p < 0.0001). Incorporating ALC into the diet significantly reduced plasma TC and LDL-C levels, downregulated genes involved in cholesterol synthesis, such as sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy-3-methyl-glutaryl-CoA reductase, and upregulated low-density lipoprotein receptor expression. ALC supplementation substantially lowered plasma TC levels and inhibited atherosclerosis in LDLR-/- mice. ALC reduced atherosclerotic plaque formation by lowering plasma cholesterol levels via suppression of SREBP2-mediated cholesterol synthesis, thus suggesting that ALC is a potential therapeutic target for ASCVD.
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