Endogenous nitric oxide is implicated in the regulation of lipolysis through antioxidant-related effect

We studied the influence of nitric oxide (NO) endogenously produced by adip ocytes in lipolysis regulation. Diphenyliodonium (DPI), a nitric oxide synt hase (NOS) inhibitor, was found to completely suppress NO synthesis in inta ct adipocytes and was thus used in lipolysis experiments. DPI was found to decrease both basal and dibutyryl cAMP (DBcAMP)-stimulated lipolysis. Inhib ition of DBcAMP-stimulated lipolysis by DPI was prevented by S-nitroso-N-ac etylpenicillamine (SNAP), a NO donor. This antilipolytic effect of DPI was also prevented by two antioxidants, ascorbate or diethyldithiocarbamic acid (DDC). Preincubation of isolated adipocytes with DPI (30 min) before expos ure to DBcAMP almost completely abolished the stimulated lipolysis. Additio n of SNAP or antioxidant during DPI preincubation restored the lipolytic re sponse to DBcAMP, whereas no preventive effects were observed when these co mpounds were added simultaneously to DBcAMP. Exposure of isolated adipocyte s to an extracellular generating system of oxygen species (xanthine/xanthin e oxidase) or to H2O2 also resulted in an inhibition of the lipolytic respo nse to DBcAMP. H2O2 or DPI decreased cAMP-dependent protein kinase (PKA) ac tivation. The DPI effect on PKA activity was prevented by SNAP, ascorbate, or DDC. These results provide clear evidence that 1) the DPI antilipolytic effect is related to adipocyte NOS inhibition leading to PKA alterations, a nd 2) endogenous NO is required for the cAMP lipolytic process through anti oxidant-related effect.