A nitric oxide-mediated mechanism regulates lipolysis in human adipose tissue in vivo

1 Possible nitric oxide (NO)-mediated effects on lipolysis were investigate d in vivo in human subcutaneous adipose tissue using microdialysis, as well as in vitro on isolated fat cells of non-obese, healthy volunteers. NO don ors were added to the ingoing dialysate solvents. 2 Changes in lipolysis and local blood flow were investigated by measuring glycerol levels and ethanol ratios, respectively, in the microdialysates. 3 It was shown that the NO synthase inhibitor, N-G-monomethyl L-arginine (L -NMMA), but not the biologically inactive enantiomer N-G-monomethyl D-argin ine (D-NMMA), increased glycerol levels in the microdialysates without caus ing a change of local blood flow. In addition, L-NMMA increased glycerol le vels in the microdialysate when local blood flow was stimulated with hydral azine. 4 Nitric oxide gas as well as the NO donor, nitroglycerine, reduced glycero l release from isolated adipocytes in vitro. 5 Expression of inducible nitric oxide synthase (iNOS) in human adipose tis sue was shown by Western blot analysis. Biologically active NOS was demonst rated by measuring total enzymatic activity. 6 In conclusion, the data demonstrate that inhibition of NO release in subc utaneous adipose tissue results in an increased lipolysis in vivo. These ef fects, which were also observed in vitro, are independent of local blood fl ow changes. Furthermore, the demonstration of enzymatic NOS activity and th e expression of inducible nitric oxide synthase (iNOS) in adipose tissue in dicate that locally synthesized NO may play a role in the physiological con trol of lipolysis in human adipose tissue.