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.
Nakamura
Jiro
J
Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305-8577, Japan. jnakamura@sakura.cc.tsukuba.ac.jp
Okamura
Naomichi
N
Kawakami
Yasushi
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D008066:Lipolysis / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D020889:Rolipram / Q000494:pharmacology; D013217:Starvation / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015363:Quinolones; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C021294:cilostamide; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram