Augmentation of lipolysis in adipocytes from fed rats, but not from starved rats, by inhibition of rolipram-sensitive phosphodiesterase 4.

The sensitivity of adipocytes to lipolytic agents is increased after starvation. In this study, we found that LY294002, an inhibitor of phosphatidylinositol-3 kinase (PI3K), in the concentration of more than 50 microM potentiates lipolysis induced by adenosine deaminase in adipocytes from fed rats (f-adipocytes), but not from starved rats (s-adipocytes). It also enhanced the sensitivity to lipolytic action of isoproterenol in f-adipocytes much more than s-adipocytes. The target of LY294002 may be an anti-lipolytic regulator expressed in response to food intake. Since another PI3K inhibitor, wortmannin, or a phosphodiesterase 3 (PDE3) inhibitor, cilostamide, failed to cause any specific effect to f-adipocytes, the PI3K-PDE3B pathway cannot be a target of LY294002. We found that LY294002 inhibits efficiently the cytoplasmic PDE activity of adipocytes. Rolipram, a specific inhibitor of PDE4, also inhibited the cytoplasmic PDE and caused a preferential increase of lipolysis in f-adipocytes. LY294002 blunted the actions of rolipram on lipolysis and the PDE activity. LY294002 accelerated protein kinase A activation. These data suggest that the rolipram-sensitive PDE4 is an anti-lipolytic enzyme expressed according to food intake. LY294002 may potentiate lipolysis through inhibition of the PDE4.