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

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, inc...

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Bibliographic Details
Published in:The Journal of biological chemistry 2018-01, Vol.293 (3), p.973-983
Main Authors: Kuo, Andrew, Lee, Monica Y., Yang, Kui, Gross, Richard W., Sessa, William C.
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
cAMP
Caveolin
Caveolin 1 - genetics
Caveolin 1 - metabolism
Cell Biology
Cell Line
Cells, Cultured
Cyclic AMP - metabolism
droplets
Endothelial Cells - metabolism
endothelium
Epoprostenol - pharmacology
Lipid Metabolism - drug effects
lipolysis
Lipolysis - drug effects
Mass Spectrometry
Mice
Mice, Mutant Strains
Phosphorylation
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA117.000980