Key result
Nitrosothiols stimulate basal lipolysis via phosphodiesterase inhibition, whereas NO gas and PAPA-NONOate inhibit stimulated lipolysis by reducing hormone-sensitive lipase activity.
Nitric oxide and related redox species regulate white adipose tissue lipolysis through distinct mechanisms involving phosphodiesterase and hormone-sensitive lipase.
Should not alter clinical approaches to lipolysis or obesity; leaves open redox-targeted therapies pending human studies.
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.
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Gaudiot et al. (1998) studied this question. Nitric oxide donors (SNAP, S-nitrosoglutathione, PAPA-NONOate, NO gas) was evaluated on Basal and stimulated lipolysis. Nitrosothiols stimulate basal lipolysis via phosphodiesterase inhibition, whereas NO gas and PAPA-NONOate inhibit stimulated lipolysis by reducing hormone-sensitive lipase activity.
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