Natriuretic peptide-dependent lipolysis in fat cell is a primate specificity

We have recently demonstrated that natriuretic peptides (NPs), known for their regulation of blood pressure via membrane guanylyl cyclase (GC) receptors, are lipolytic in human adipose tissue. In this study we compared the NP control of lipolysis in adipocytes from man, non-human primates (macaque), rodents (rat, mouse, hamster) and non-rodent mammals (rabbit, dog). Isolated adipocytes from these species were exposed to increasing concentrations of atrial NP (ANP) or isoproterenol (ß adrenergic agonist). While isoproterenol was lipolytic in all the species, ANP only enhanced lipolysis in man and macaque adipocytes. In primate fat cells NP-induced lipolysis involved a cGMP dependent pathway. Binding studies and real time quantitative PCR assays revealed that rat adipocyte expressed a higher density of NP receptors compared with human but with a different subtype pattern of expression, GC-A receptors predominate in human fat cells. This was also confirmed by the weak GC activity stimulation and the reduced cGMP formation under ANP exposure in rat adipocytes compared with human fat cells. In conclusion, NP-induced lipolysis is a primate specificity, adipocytes from ANP-non-responsive species present a predominance of "clearance" receptor and a very low expression of "biologically active" receptor.