Reduced PDE4 expression and activity contributes to enhanced catecholamine-induced cAMP accumulation in adipocytes from FOXC2 transgenic mice

Gronning, L. M., Baillie, G. S. , Cederberg, A., Lynch, M. J., Houslay, M. D., Enerback, S. and Tasken, K. (2006) Reduced PDE4 expression and activity contributes to enhanced catecholamine-induced cAMP accumulation in adipocytes from FOXC2 transgenic mice. FEBS Letters, 580(17), pp. 4126-4130. (doi:10.1016/j.febslet.2006.06.058)

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Abstract

Overexpression of forkhead transcription factor FOXC2 in white adipose tissue (WAT) leads to a lean phenotype resistant to diet-induced obesity. This is due, in part, to enhanced catecholamine-induced cAMP-PKA signaling in FOXC2 transgenic mice. Here we show that rolipram treatment of adipocytes from FOXC2 transgenic mice did not increase isoproterenol-induced cAMP accumulation to the same extent as in wild type cells. Accordingly, phosphodiesterase-4 (PDE4) activity was reduced by 75% and PDE4A5 protein expression reduced by 30–50% in FOXC2 transgenic WAT compared to wild type. Thus, reduced PDE4 activity in adipocytes from FOXC2 transgenic mice contributes to amplified β-AR induced cAMP responses observed in these cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles and Baillie, Professor George
Authors: Gronning, L. M., Baillie, G. S., Cederberg, A., Lynch, M. J., Houslay, M. D., Enerback, S., and Tasken, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:FEBS Letters
Publisher:Elsevier
ISSN:0014-5793
ISSN (Online):1873-3468
Published Online:30 June 2006

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
208361PDE4 cAMP phosphodiesterses: intracellular targeting, SH3 domain interaction and phosphorylation by stress kinasesMiles HouslayMedical Research Council (MRC)G8604010Institute of Neuroscience and Psychology
294081PDE4 Cyclic AMP phosphodiesterasesMiles HouslayMedical Research Council (MRC)G8604010Institute of Neuroscience and Psychology
30692Molecular interaction between receptor signal transduction systems involving guanine nucleotide regulatory proteinsMiles HouslayMedical Research Council (MRC)G8604010Institute of Neuroscience and Psychology
343641PDE4 cAMP phosphodiesterases - intracellular targeting, SH3 Domain Interaction & phosphorylation by stress kinasesMiles HouslayMedical Research Council (MRC)G8604010Institute of Neuroscience and Psychology
97371Programme Grant (PG 8604010) Supplementation (Equipment). Molecular interaction between receptor transduction systems involving guanine nuclMiles HouslayMedical Research Council (MRC)G8604010Institute of Neuroscience and Psychology