2. Academic Validation
  3. Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice

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

  • Nat Commun. 2024 Sep 27;15(1):8273. doi: 10.1038/s41467-024-52621-x.
Yanjie Tan # 1,  Zhenzhou Huang # 1,  Yi Jin 2,  Jiaying Wang 1,  Hongjun Fan 1,  Yangyang Liu 1,  Liang Zhang 2,  Yue Wu 1,  Peiwei Liu 1,  Tianliang Li 1,  Jie Ran 1,  He Tian 3,  Sin Man Lam 3 4,  Min Liu 5,  Jun Zhou 6 7,  Yunfan Yang 8
Affiliations

Affiliations

  • 1 Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, 250014, Jinan, China.
  • 2 Metabolism and Disease Research Centre, Central Hospital Affiliated to Shandong First Medical University, 250013, Jinan, China.
  • 3 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.
  • 4 LipidALL Technologies Company Limited, 213022, Changzhou, China.
  • 5 Laboratory of Tissue Homeostasis, Haihe Laboratory of Cell Ecosystem, 300462, Tianjin, China.
  • 6 Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, 250014, Jinan, China. junzhou@sdnu.edu.cn.
  • 7 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 300071, Tianjin, China. junzhou@sdnu.edu.cn.
  • 8 Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 250012, Jinan, China. yunfanyang@sdu.edu.cn.
  • # Contributed equally.
PMID: 39333556 DOI: 10.1038/s41467-024-52621-x
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.

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