Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice

Nabil E. Boutagy, Ana Gamez-Mendez, Joseph Wm Fowler, Hanming Zhang, Bal K. Chaube, Enric Esplugues, Andrew Kuo, Sungwoon Lee, Daiki Horikami, Jiasheng Zhang, Kathryn M. Citrin, Abhishek K. Singh, Brian G. Coon, Monica Y. Lee, Yajaira Suarez, Carlos Fernandez-Hernando, William C. Sessa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD affects endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.

Original languageEnglish
Article number170453
JournalJournal of Clinical Investigation
Volume134
Issue number4
DOIs
Publication statusPublished - 15 Feb 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024, Boutagy et al.

All Science Journal Classification (ASJC) codes

  • General Medicine

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