Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity.
We have recently demonstrated that natriuretic peptides (NPs), which are known for 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 humans, nonhuman primates (macaques), rodents (rats, mice, hamsters), and nonrodent mammals (rabbits, dogs). Isolated adipocytes from these species were exposed to increasing concentrations of atrial NP (ANP) or isoproterenol (beta-adrenergic agonist). Although isoproterenol was lipolytic in all of the species, ANP only enhanced lipolysis in human 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 adipocytes expressed a higher density of NP receptors compared with humans but with a different subtype pattern of expression; type-A GC 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, and adipocytes from ANP-nonresponsive species present a predominance of "clearance" receptors and very low expression of "biologically active" receptors.
Sengenès
Coralie
C
INSERM U317, Laboratory of Medical and Clinical Pharmacology, Division of Medicine, National Institute of Health and Medical Research, Unité 317, 37 Allées Jules Guesde, 31073 Toulouse Cedex, France. corasengenes@yahoo.com
Zakaroff-Girard
Alexia
A
Moulin
Agnès
A
Berlan
Michel
M
Bouloumié
Anne
A
Lafontan
Max
M
Galitzky
Jean
J
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000502:physiology*; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000502:physiology*; D011323:Primates / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics; D012377:Rodentia; D013045:Species Specificity
D045283:Natriuretic Agents; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007545:Isoproterenol