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Circ Res. 2017 Apr 14;120(8):1289-1297. doi: 10.1161/CIRCRESAHA.116.310498. Epub 2017 Jan 24.

Lipid Droplet Biogenesis and Function in the Endothelium.

Author information

1
From the Vascular Biology and Therapeutics Program (A.K., M.Y.L., W.C.S.), Department of Pharmacology (M.Y.L., W.C.S.), and Department of Cell Biology (A.K.), Yale University, School of Medicine, New Haven, CT.
2
From the Vascular Biology and Therapeutics Program (A.K., M.Y.L., W.C.S.), Department of Pharmacology (M.Y.L., W.C.S.), and Department of Cell Biology (A.K.), Yale University, School of Medicine, New Haven, CT. william.sessa@yale.edu.

Abstract

RATIONALE:

Fatty acids (FA) are transported across the capillary endothelium to parenchymal tissues. However, it is not known how endothelial cells (EC) from large vessels process a postprandial surge of FA.

OBJECTIVE:

This study was designed to characterize lipid droplet (LD) formation in EC by manipulating pathways leading to the formation and degradation of LD. In addition, several functions of LD-derived FA were assessed.

METHODS AND RESULTS:

LD were present in EC lining the aorta after the peak in plasma triglycerides initiated by a gavage of olive oil in mice, in vivo. Similarly, in isolated aorta, oleic acid treatment generates LD in EC ex vivo. Cultured EC readily form LD largely via the enzyme DGAT (diacylglycerol O-acyltransferase 1) and degrade LD via ATGL (adipocyte triglyceride lipase) after FA loading. Functionally, LD-derived FA are dynamically regulated and function to protect EC from lipotoxic stress and provide FA for metabolic needs.

CONCLUSIONS:

Our results delineate endothelial LD dynamics for the first time in vivo and in vitro. Moreover, LD formation protects EC from lipotoxic stress, regulates EC glycolysis, and provides a source of FA for adjacent cells in the vessel wall or tissues.

KEYWORDS:

endothelial function; endothelium; fatty acids; lipid droplet; lipids; metabolism; triglycerides

PMID:
28119423
PMCID:
PMC5392152
DOI:
10.1161/CIRCRESAHA.116.310498
[Indexed for MEDLINE]
Free PMC Article

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