title: Reduced PDE4 expression and activity contributes to enhanced catecholamine-induced cAMP accumulation in adipocytes from FOXC2 transgenic mice.
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 beta-AR induced cAMP responses observed in these cells.
authors.affiliation: Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway. l.m.g.wang@biotek.uio.no
authors.forename: Line M
authors.initials: LM
authors.lastname: Grønning
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.forename: Anna
authors.initials: A
authors.lastname: Cederberg
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lynch
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.forename: Sven
authors.initials: S
authors.lastname: Enerbäck
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D051858:Forkhead Transcription Factors; D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; C082078:mesenchyme fork head 1 protein; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D007545:Isoproterenol