Natriuretic peptides:: a new lipolytic pathway in human adipocytes

被引:396
作者
Sengenès, C [1 ]
Berlan, M [1 ]
De Glisezinski, I [1 ]
Lafontan, M [1 ]
Galitzky, J [1 ]
机构
[1] Fac Med Toulouse, INSERM, U317, Lab Pharmacol Med & Clin, F-31073 Toulouse, France
关键词
human fat cells; ANP; BNP; lipolysis; microdialysis;
D O I
10.1096/fj.14.10.1345
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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 alpha(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.
引用
收藏
页码:1345 / 1351
页数:7
相关论文
共 30 条
[1]  
ANANDSRIVASTAVA MB, 1990, J BIOL CHEM, V265, P8566
[2]  
ATHONSEN MW, 1998, J BIOL CHEM, V273, P215
[3]  
BERLAN M, 1980, J PHYSIOL-PARIS, V76, P133
[4]   RADIOMETRIC ASSAYS FOR GLYCEROL, GLUCOSE, AND GLYCOGEN [J].
BRADLEY, DC ;
KASLOW, HR .
ANALYTICAL BIOCHEMISTRY, 1989, 180 (01) :11-16
[5]   A RAPID AND POTENT NATRIURETIC RESPONSE TO INTRAVENOUS-INJECTION OF ATRIAL MYOCARDIAL EXTRACT IN RATS [J].
DEBOLD, AJ ;
BORENSTEIN, HB ;
VERESS, AT ;
SONNENBERG, H .
LIFE SCIENCES, 1981, 28 (01) :89-94
[6]   Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3) [J].
Degerman, E ;
Belfrage, P ;
Manganiello, VC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (11) :6823-6826
[7]   cGMP-inhibited phosphodiesterases (PDE3 gene family) [J].
Degerman, E ;
Belfrage, P ;
Manganiello, VC .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1996, 24 (04) :1010-1014
[8]   LOCALIZATION OF ATRIAL-NATRIURETIC-FACTOR RECEPTORS IN THE MESENTERIC ARTERIAL BED - COMPARISON WITH ANGIOTENSIN-II AND ENDOTHELIN RECEPTORS [J].
DELEON, H ;
BONHOMME, MC ;
THIBAULT, G ;
GARCIA, R .
CIRCULATION RESEARCH, 1995, 77 (01) :64-72
[9]  
GSKE R, 1989, BIOMED RES, V10, P463
[10]   IMMUNOCYTOCHEMICAL LOCALIZATION, BINDING, AND EFFECTS OF ATRIAL NATRIURETIC PEPTIDE IN RAT ADIPOCYTES [J].
JEANDEL, L ;
OKAMURA, H ;
BELLESISLES, M ;
CHABOT, JG ;
DIHL, F ;
MOREL, G ;
KELLY, PA ;
HEISLER, S .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1989, 62 (01) :69-78