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

• 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.

Keyword

3'

5'-Cyclic-Nucleotide Phosphodiesterase

antagonists & inhibitors

metabolism

Adipocytes

cytology

metabolism

Adipose Tissue

cytology

metabolism

Adrenergic beta-Agonists

pharmacology

Animals

Catecholamines

pharmacology

Cells

Cultured

Cyclic AMP

biosynthesis

genetics

Forkhead Transcription Factors

biosynthesis

genetics

Gene Expression

genetics

Isoproterenol

pharmacology

Mice

Mice

Transgenic

Obesity

genetics

metabolism

Phosphodiesterase Inhibitors

pharmacology

Receptors

Adrenergic

beta

metabolism

Rolipram

pharmacology

Signal Transduction

drug effects

physiology

Publication and Content Type

ref (subject category)

art (subject category)