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ORIGINAL RESEARCH article

Front. Nutr.
Sec. Nutrition and Metabolism
Volume 11 - 2024 | doi: 10.3389/fnut.2024.1509577
This article is part of the Research Topic Therapeutic Potential of Food-Derived Bioactive Compounds and Endogenous Metabolites for Diabetes, Cardiovascular, and Cerebrovascular Diseases View all articles

Acetyl-L-carnitine ameliorates atherosclerosis in LDLR -/-mice by modulating cholesterol metabolism through SREBP2-dependent cholesterol biosynthesis

Provisionally accepted
Jingci Xing Jingci Xing 1Zhi Yong Du Zhi Yong Du 1Fan Li Fan Li 1,2Yu Wang Yu Wang 1Zihan Zhang Zihan Zhang 1Xiaoqian Gao Xiaoqian Gao 1Lijie Han Lijie Han 1Xuechun Sun Xuechun Sun 1Haili Sun Haili Sun 1Yunhui Du Yunhui Du 1Chaowei Hu Chaowei Hu 1Huahui Yu Huahui Yu 1Yanwen Qin Yanwen Qin 1*
  • 1 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
  • 2 School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong Province, China

The final, formatted version of the article will be published soon.

    Background: 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 remain 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 on 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. Results: 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.

    Keywords: Atheroscelrosis, Cholesterol metabloism, acetyl-l-carnitine (ALC), SREBP2, HMGCR

    Received: 11 Oct 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Xing, Du, Li, Wang, Zhang, Gao, Han, Sun, Sun, Du, Hu, Yu and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yanwen Qin, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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