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J Biol Chem. 2018 Jan 19;293(3):973-983. doi: 10.1074/jbc.RA117.000980. Epub 2017 Dec 4.

Caveolin-1 regulates lipid droplet metabolism in endothelial cells via autocrine prostacyclin-stimulated, cAMP-mediated lipolysis.

Kuo A1,2, Lee MY1,3, Yang K4,5, Gross RW4,5, Sessa WC6,3.

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From the Vascular Biology and Therapeutics Program and.
Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Departments of Pharmacology and.
the Department of Medicine and Developmental Biology, Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, and.
the Department of Chemistry, Washington University, St. Louis, Missouri 63130.
From the Vascular Biology and Therapeutics Program and


Lipid droplets (LD) are dynamic organelles involved in intracellular lipid metabolism in almost all eukaryotic cells, and LD-associated proteins tightly regulate their dynamics. One LD coat protein is caveolin-1 (Cav-1), an essential component for caveola assembly in highly differentiated cells, including adipocytes, smooth muscle cells, and endothelial cells (EC). However, the role of Cav-1 in LD dynamics is unclear. Here we report that EC lacking Cav-1 exhibit impaired LD formation. The decreased LD formation is due to enhanced lipolysis and not caused by reduced triglyceride synthesis or fatty acid uptake. Mechanistically, the absence of Cav-1 increased cAMP/PKA signaling in EC, as indicated by elevated phosphorylation of hormone-sensitive lipase and increased lipolysis. Unexpectedly, we also observed enhanced autocrine production of prostaglandin I2 (PGI2, also called prostacyclin) in Cav-1 KO EC, and this PGI2 increase appeared to stimulate cAMP/PKA pathways, contributing to the enhanced lipolysis in Cav-1 KO cells. Our results reveal an unanticipated role of Cav-1 in regulating lipolysis in non-adipose tissue, indicating that Cav-1 is required for LD metabolism in EC and that it regulates cAMP-dependent lipolysis in part via the autocrine production of PGI2.


Caveolin; cAMP; droplets; endothelium; lipolysis

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