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...

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Main Authors: Peter B. Snyder, James M. Esselstyn, Kate Loughney, Sharon L. Wolda, Vincent A. Florio
Format: Article
Language:English
Published: Elsevier 2005-03-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520340347
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author Peter B. Snyder
James M. Esselstyn
Kate Loughney
Sharon L. Wolda
Vincent A. Florio
author_facet Peter B. Snyder
James M. Esselstyn
Kate Loughney
Sharon L. Wolda
Vincent A. Florio
author_sort Peter B. Snyder
collection DOAJ
description 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.
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spelling doaj.art-562ce4ad18764bbebb45e15e2e676b402022-12-21T21:25:47ZengElsevierJournal of Lipid Research0022-22752005-03-01463494503The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysisPeter B. Snyder0James M. Esselstyn1Kate Loughney2Sharon L. Wolda3Vincent A. Florio4ICOS Corporation, Bothell, WA 98021ICOS Corporation, Bothell, WA 98021ICOS Corporation, Bothell, WA 98021ICOS Corporation, Bothell, WA 98021ICOS Corporation, Bothell, WA 98021This 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.http://www.sciencedirect.com/science/article/pii/S0022227520340347cilostamiderolipramtriglyceride
spellingShingle Peter B. Snyder
James M. Esselstyn
Kate Loughney
Sharon L. Wolda
Vincent A. Florio
The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
Journal of Lipid Research
cilostamide
rolipram
triglyceride
title The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
title_full The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
title_fullStr The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
title_full_unstemmed The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
title_short The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
title_sort role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
topic cilostamide
rolipram
triglyceride
url http://www.sciencedirect.com/science/article/pii/S0022227520340347
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