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INSERM U 317 and Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 31073 Toulouse Cedex, France
1Correspondence: INSERM U317, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 Allées Jules Guesde, 31073 Toulouse Cedex, France. E-mail: galitzky{at}cict.fr
Atrial natriuretic peptide (ANP) receptors have been described on
rodent adipocytes and expression of their mRNA is found in human
adipose tissue. However, no biological effects associated with the
stimulation of these receptors have been reported in this tissue. A
putative lipolytic effect of natriuretic peptides was investigated in
human adipose tissue. On isolated fat cells, ANP and brain natriuretic
peptide (BNP) stimulated lipolysis as much as isoproterenol, a
nonselective ß-adrenergic receptor agonist, whereas C-type
natriuretic peptide (CNP) had the lowest lipolytic effect. In
situ microdialysis experiments confirmed the potent lipolytic
effect of ANP in abdominal s.c. adipose tissue of healthy subjects. A
high level of ANP binding sites was identified in human adipocytes. The
potency order defined in lipolysis (ANP > BNP > CNP) and
the ANP-induced cGMP production sustained the presence of type A
natriuretic peptide receptor in human fat cells. Activation or
inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insulin
and OPC 3911, respectively) did not modify ANP-induced lipolysis
whereas the isoproterenol effect was decreased or increased. Moreover,
inhibition of adenylyl cyclase activity (using a mixture of
2-adrenergic and adenosine A1 agonists receptors) did
not change ANP- but suppressed isoproterenol-induced lipolysis. The
noninvolvement of the PDE-3B was finally confirmed by measuring its
activity under ANP stimulation. Thus, we demonstrate that natriuretic
peptides are a new pathway controlling human adipose tissue lipolysis
operating via a cGMP-dependent pathway that does not involve PDE-3B
inhibition and cAMP production.—Sengenès, C., Berlan, M., De
Glisezinski, I., Lafontan, M., Galitzky, J. Natriuretic peptides: a
new lipolytic pathway in human adipocytes.
Key Words: human fat cells • ANP • BNP • lipolysis • microdialysis
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