Modulation of white adipose tissue lipolysis by nitric oxide.
In isolated adipocytes, the nitrosothiols S-nitroso-N-acetyl-penicillamine (SNAP) and S-nitrosoglutathione stimulate basal lipolysis, whereas the nitric oxide (NO.) donor 1-propamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA-NONOate) or NO gas have no effect. The increase in basal lipolysis due to nitrosothiols was prevented by dithiothreitol but not by a guanylate cyclase inhibitor. In addition the cyclic GMP-inhibited low Km, cyclic AMP phosphodiesterase activity was inhibited by SNAP suggesting that SNAP acting as NO+ donor increases basal lipolysis through a S-nitrosylation mediated inhibition of phosphodiesterase. Contrasting with these findings, SNAP reduced both isoproterenol-stimulated lipolysis and cyclic AMP production, whereas it failed to modify forskolin-, dibutyryl cyclic AMP-, or isobutylmethylxanthine-stimulated lipolysis, suggesting that SNAP interferes with the beta-adrenergic signal transduction pathway upstream the adenylate cyclase. In contrast with SNAP, PAPA-NONOate or NO gas inhibited stimulated lipolysis whatever the stimulating agents used without altering cyclic AMP production. Moreover PAPA-NONOate slightly reduces (30%) the hormone-sensitive lipase (HSL) activity indicating that stimulated lipolysis inhibition by NO. is linked to both inhibition of the HSL activity and the cyclic AMP-dependent activation of HSL. These data suggest that NO. or related redox species like NO+/NO- are potential regulators of lipolysis through distinct mechanisms.
Gaudiot
N
N
Department of Biochemistry, INSERM CJF 94--02, Faculté de Médecine de Paris-Ouest, Universite René Descartes, Paris, France.
Jaubert
A M
AM
Charbonnier
E
E
Sabourault
D
D
Lacasa
D
D
Giudicelli
Y
Y
Ribière
C
C
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology; D006834:Hydrazines / Q000737:chemistry; D008066:Lipolysis; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009603:Nitroso Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives / Q000737:chemistry
D006834:Hydrazines; D009603:Nitroso Compounds; C112653:PAPA NONOate; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine; D006152:Cyclic GMP