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

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

FEBS letters (2006-07-11)
Line M Grønning, George S Baillie, Anna Cederberg, Martin J Lynch, Miles D Houslay, Sven Enerbäck, Kjetil Taskén
ANOTACE

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 beta-AR induced cAMP responses observed in these cells.

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Sigma-Aldrich
Rolipram, A cell-permeable, selective inhibitor of cAMP-specific phosphodiesterase (PDE IV; IC₅₀ = 800 nM).
Sigma-Aldrich
Cilostamide, A cell-permeable selective inhibitor of cGMP-inhibited phosphodiesterase (PDE III; IC₅₀ = 70 nM).