Differential regulation of atrial natriuretic peptide- and adrenergic receptor-dependent lipolytic pathways in human adipose tissue
Abstract
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 α2-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 a β-AR agonist or of epinephrine were unchanged.
Insulin was without any effect on ANP-induced lipolysis and α2-AR-mediated antilipolysis, while it reduced β-AR-induced lipolysis. The ANP-dependent lipolytic pathway undergoes desensitization in vitro and in situ.
Insulin had no inhibitory effect on either ANP- or α2-AR-dependent pathways, while it counteracted the β-AR pathway.