Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice

Yanjie Tan, Zhenzhou Huang, Yi Jin, Jiaying Wang, Hongjun Fan, Yangyang Liu, Liang Zhang, Yue Wu, Peiwei Liu, Tianliang Li, Jie Ran, He Tian, Sin Man Lam, Min Liu, Jun Zhou () and Yunfan Yang ()
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Yanjie Tan: Shandong Normal University
Zhenzhou Huang: Shandong Normal University
Yi Jin: Central Hospital Affiliated to Shandong First Medical University
Jiaying Wang: Shandong Normal University
Hongjun Fan: Shandong Normal University
Yangyang Liu: Shandong Normal University
Liang Zhang: Central Hospital Affiliated to Shandong First Medical University
Yue Wu: Shandong Normal University
Peiwei Liu: Shandong Normal University
Tianliang Li: Shandong Normal University
Jie Ran: Shandong Normal University
He Tian: Chinese Academy of Sciences
Sin Man Lam: Chinese Academy of Sciences
Min Liu: Haihe Laboratory of Cell Ecosystem
Jun Zhou: Shandong Normal University
Yunfan Yang: Shandong University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

Date: 2024
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DOI: 10.1038/s41467-024-52621-x

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