Okadaic Acid, a Bioactive Fatty Acid from Halichondria okadai, Stimulates Lipolysis in Rat Adipocytes : The Pivotal Role of Perilipin Translocation

Abstract EN

Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases.

Okadaic-acid, a 38-carbon fatty acid isolated from the black sponge Halichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes.

However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin) remain unclear.

We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release.

Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis.

Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment.

Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor), calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate okadaic-acid-induced lipolysis.

By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis.

These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.