Modulation of White Adipose Tissue Lipolysis by Nitric Oxide

• Published in: The Journal of biological chemistry 1998-05, Vol.273 (22), p.13475-13481
• Main Authors: Gaudiot, Nicolas, Jaubert, Anne-Marie, Charbonnier, Elisabeth, Sabourault, Dominique, Lacasa, Daniéle, Giudicelli, Yves, Ribiére, Catherine
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Adipose Tissue - metabolism; ADIPOSE TISSUES; AMP; C-AMP; CELLS; Cells, Cultured; CYCLIC AMP PHOSPHODIESTERASE; Cyclic GMP - physiology; ENZYME INHIBITORS; ESTERASES; GUANYLATE CYCLASE; Hydrazines - chemistry; LIPOLYSIS; LYASES; NITRIC OXIDE; Nitric Oxide - chemistry; Nitric Oxide - metabolism; Nitric Oxide - physiology; NITROSO COMPOUNDS; Nitroso Compounds - chemistry; NITROSOTHIOLS; ORGANIC NITROGEN COMPOUNDS; Oxidation-Reduction; Penicillamine - analogs & derivatives; Penicillamine - chemistry; PHOSPHORIC DIESTER HYDROLASES; QUINOXALINES; RATS; REGULATION
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.22.13475

In isolated adipocytes, the nitrosothiolsS-nitroso-N-acetyl-penicillamine (SNAP) andS-nitrosoglutathione stimulate basal lipolysis, whereas the nitric oxide (NOċ) 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 β-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 NOċ is linked to both inhibition of the HSL activity and the cyclic AMP-dependent activation of HSL. These data suggest that NOċ or related redox species like NO+/NO− are potential regulators of lipolysis through distinct mechanisms.