J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on March 1, 2005

Papers In Press, published online ahead of print December 16, 2004
J. Lipid Res., doi:10.1194/jlr.M400362-JLR200
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Submitted on September 23, 2004
Revised on November 29, 2004
Accepted on December 7, 2004

The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis

Peter B. Snyder, James M. Esselstyn, Kate Loughney, Sharon L. Wolda, and Vincent A. Florio

ICOS Corp., Bothell, WA 98021

Corresponding Author: psnyder{at}icos.com

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 type 2 phosphodiesterase (PDE2), had no effect on lipolysis in either cultured murine 3T3-L1 adipocytes or human adipocytes. Inhibition of type 3 phosphodiesterase (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 type 4 phosphodiesterase (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.


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