Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice
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.
Authors
- Jie Ran (ORCID: https://orcid.org/0000-0002-0744-7126)
- He Tian (ORCID: https://orcid.org/0000-0002-5388-0297)
- Sin Man Lam (ORCID: https://orcid.org/0000-0001-9037-904X)
- Zhenzhou Huang (ORCID: https://orcid.org/0000-0002-6635-2530)
- Yunfan Yang (ORCID: https://orcid.org/0000-0002-5266-7208)
- Peiwei Liu (ORCID: https://orcid.org/0000-0001-5597-2200)
- Jun Zhou (ORCID: https://orcid.org/0000-0003-3131-7804)
- Hongjun Fan (ORCID: https://orcid.org/0000-0003-3406-6932)
- Jiaying Wang (ORCID: https://orcid.org/0000-0002-9720-6181)
- Yue Wu (ORCID: https://orcid.org/0000-0001-5598-6215)
- Yi Jin (ORCID: https://orcid.org/0000-0001-8094-6899)
- Tianliang Li (ORCID: https://orcid.org/0000-0003-2673-0549)
- Min Liu (ORCID: https://orcid.org/0009-0003-8010-3084)
- Liang Zhang (ORCID: https://orcid.org/0000-0001-8888-9550)
- Yanjie Tan
- Yangyang Liu (ORCID: https://orcid.org/0009-0000-6334-815X)
Institutions
- Shandong University (CN)
- Chinese Academy of Sciences (CN)
- Nankai University (CN)
- Shandong Normal University (CN)
- Jinan Central Hospital (CN)
- LipidALL Technologies (China) (CN)
- Institute of Genetics and Developmental Biology (CN)
- Shandong First Medical University (CN)
- Tianjin haihe hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1038/s41467-024-52621-x
- Citations
- 25
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 7.37