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 α 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 a β-AR agonist or of epinephrine were unchanged. Insulin was without any effect on ANP-induced lipolysis and α 2-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 α 2-AR–dependent pathways, while it counteracted the β-AR pathway.