Natriuretic peptides: a new lipolytic pathway in human adipocytes

Atrial natriuretic peptide (ANP) receptors have been described on rodent ad ipocytes and expression of their mRNA is found in human adipose tissue. How ever, no biological effects associated with the stimulation of these recept ors have been reported in this tissue. A putative lipolytic effect of natri uretic peptides was investigated in human adipose tissue. On isolated fat c ells, ANP and brain natriuretic peptide (BNP) stimulated lipolysis as much as isoproterenol, a nonselective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. In situ m icrodialysis experiments confirmed the potent lipolytic effect of ANP in ab dominal s.c. adipose tissue of healthy subjects. A high level of ANP bindin g sites was identified in human adipocytes. The potency order defined in li polysis (ANP > BNP > CNP) and the ANP-induced cGMP production sustained the presence of type A natriuretic peptide receptor in human fat cells. Activa tion or inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insu lin and OPC 3911, respectively) did not modify ANP-induced lipolysis wherea s the isoproterenol effect was decreased or increased. Moreover, inhibition of adenylyl cyclase activity (using a mixture of alpha(2)-adrenergic and a denosine A1 agonists receptors) did not change ANP- but suppressed isoprote renol-induced lipolysis. The noninvolvement of the PDE-3B was finally confi rmed by measuring its activity under ANP stimulation. Thus, we demonstrate that natriuretic peptides are a new pathway controlling human adipose tissu e lipolysis operating via a cGMP-dependent pathway that does not involve PD E-3B inhibition and cAMP production.