MODULATION OF WHITE ADIPOSE-TISSUE LIPOLYSIS BY NITRIC-OXIDE

In isolated adipocytes, the nitrosothiols S-nitroso-N-acetyl-penicilla mine (SNAP) and S-nitrosoglutathione stimulate basal lipolysis, wherea s the nitric oxide (NO) donor 1-propamine, 3-(2-hydroxy-2-nitroso-1-pr opylhydrazine) (PAPA-NONOate) or NO gas have no effect. The increase i n 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 lipo lysis through a S-nitrosylation mediated inhibition of phosphodiestera se, Contrasting with these findings, SNAP reduced both isoproterenol-s timulated lipolysis and cyclic AMP production, whereas it failed to mo dify forskolin-, dibutyryl cyclic AMP-, or isobutylmethylxanthine-stim ulated lipolysis, suggesting that SNAP interferes with the beta-adrene rgic signal transduction pathway upstream the adenylate cyclase. In co ntrast with SNAP, PAPA-NONOate or NO gas inhibited stimulated lipolysi s whatever the stimulating agents used without altering cyclic AMP pro duction. Moreover PAPA-NONOate slightly reduces (30%) the hormone-sens itive lipase (HSL) activity indicating that stimulated lipolysis inhib ition by NO is linked to both inhibition of the HSL activity and the c yclic AMP-dependent activation of HSL. These data suggest that NO or r elated redox species libe NO+/NO- are potential regulators of lipolysi s through distinct mechanisms.