Modulation of White Adipose Tissue Lipolysis by Nitric Oxide

Abstract In isolated adipocytes, the nitrosothiolsS-nitroso-N-acetyl-penicillamine (SNAP) andS-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 K m, 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 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.