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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.

Author information

1
From the Vascular Biology and Therapeutics Program and.
2
Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
3
Departments of Pharmacology and.
4
the Department of Medicine and Developmental Biology, Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, and.
5
the Department of Chemistry, Washington University, St. Louis, Missouri 63130.
6
From the Vascular Biology and Therapeutics Program and william.sessa@yale.edu.

Abstract

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.

KEYWORDS:

Caveolin; cAMP; droplets; endothelium; lipolysis

PMID:
29203526
PMCID:
PMC5777268
DOI:
10.1074/jbc.RA117.000980
[Indexed for MEDLINE]
Free PMC Article

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