The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis.
This study assessed the effects of selective inhibitors of 3',5'-cyclic nucleotide phosphodiesterases (PDEs) on adipocyte lipolysis. IC224, a selective inhibitor of type 1 phosphodiesterase (PDE1), suppressed lipolysis in murine 3T3-L1 adipocytes (69.6 +/- 5.4% of vehicle control) but had no effect in human adipocytes. IC933, a selective inhibitor of PDE2, had no effect on lipolysis in either cultured murine 3T3-L1 adipocytes or human adipocytes. Inhibition of PDE3 with cilostamide moderately stimulated lipolysis in murine 3T3-L1 and rat adipocytes (397 +/- 25% and 235 +/- 26% of control, respectively) and markedly stimulated lipolysis in human adipocytes (932 +/- 7.6% of control). Inhibition of PDE4 with rolipram moderately stimulated lipolysis in murine 3T3-L1 adipocytes (291 +/- 13% of control) and weakly stimulated lipolysis in rat adipocytes (149 +/- 7.0% of control) but had no effect on lipolysis in human adipocytes. Cultured adipocytes also responded differently to a combination of PDE3 and PDE4 inhibitors. Simultaneous exposure to cilostamide and rolipram had a synergistic effect on lipolysis in murine 3T3-L1 and rat adipocytes but not in human adipocytes. Hence, the relative importance of PDE3 and PDE4 in regulating lipolysis differed in cultured murine, rat, and human adipocytes.
Snyder
Peter B
PB
ICOS Corporation, Bothell, WA 98021, USA. psnyder@icos.com
Esselstyn
James M
JM
Loughney
Kate
K
Wolda
Sharon L
SL
Florio
Vincent A
VA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000502:physiology*; D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D005092:Exonucleases / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats
D010726:Phosphodiesterase Inhibitors; D005092:Exonucleases; C022650:spleen exonuclease; D043264:Phosphodiesterase I; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4