Differential regulation of atrial natriuretic peptide- and adrenergic receptor-dependent lipolytic pathways in human adipose tissue.
The aim of the study was to investigate the regulation affecting the recently described atrial natriuretic peptide (ANP)-dependent lipolytic pathway in comparison with the adrenergic lipolytic cascade. We studied in vivo the effect of a euglycemic-hyperinsulinemic clamp on the changes occurring in the extracellular glycerol concentration (EGC) of subcutaneous adipose tissue (SCAT) during ANP or epinephrine perfusion in a microdialysis probe. Homologous desensitization and the incidence of hyperinsulinemia on the ANP- and catecholaminergic-dependent control of lipolysis were also investigated in vitro on fat cells from SCAT. When perfused in SCAT, epinephrine and ANP promoted an increase in EGC; the EGC increase was significantly lower during the clamp. The reduction of epinephrine-induced lipolysis was limited (18%) when phentolamine (an alpha(2)-adrenergic receptor [AR] antagonist) was perfused together with epinephrine. Unlike the effect of epinephrine, the response to ANP observed during the second perfusion was reduced by 32%. The increase in extracellular guanosine 3',5' -cyclic monophosphate concentration, which reflects ANP activity, was also reduced during the second perfusion. Desensitization of the lipolytic effects of ANP was observed in vitro after a 2-hour period of recovery, while the effects of alpha(2)-AR agonist or of epinephrine were unchanged. Insulin was without any effect on ANP-induced lipolysis and alpha(2)-AR-mediated antilipolysis, while it reduced beta-AR-induced lipolysis. The ANP-dependent lipolytic pathway undergoes desensitization in vitro and in situ. Insulin had no inhibitory effect on either ANP- or alpha(2)-AR-dependent pathways, while it counteracted the beta-AR pathway.
Moro
Cédric
C
Unité de Recherches sur les Obésités Inserm U586, Institut Louis Bugnard, Center Hospitalier Universitaire de Toulouse, Université Paul Sabatier, 31062 Toulouse, France.
Polak
Jan
J
Richterova
Blanka
B
Sengenès
Coralie
C
Pelikanova
Terezie
T
Galitzky
Jean
J
Stich
Vladimir
V
Lafontan
Max
M
Berlan
Michel
M
D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism*; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects
D007328:Insulin; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol; D004837:Epinephrine