Dissociation between adipose nitric oxide synthase expression and tissue metabolism.

Abstract

Nitric oxide synthase (NOS) expression in adipose tissue is increased in obese subjects. The functional relevance is not known. The objective was to compare adipose tissue metabolism between obese men with greater or lower adipose endothelial NOS (eNOS) or inducible NOS (iNOS) expression. The design was an open-labeled prospective study. The study took place at an academic clinical research center. The patients included 14 obese (32 +/- 0.6 kg/m2) and eight normal-weight (23 +/- 2 kg/m2) healthy men. Microdialysis catheters in abdominal sc adipose tissue and in vastus lateralis were perfused with N-omega-nitro-L-arginine methyl ester (L-NAME) or N-omega-nitro-D-arginine methyl ester (D-NAME). Then, incremental isoproterenol concentrations were added to the perfusate. Microdialysate glycerol was the main outcome measure. Tissue perfusion and microdialysate glycerol concentrations at baseline and during isoproterenol stimulation were similar in obese men with high or low eNOS or iNOS expression during both L-NAME and D-NAME. During D-NAME, basal and maximal isoproterenol stimulated glycerol were similar in lean and in obese men. However, in lean men, the dose-response relationship between isoproterenol and glycerol was shifted towards the left (P < 0.0001). NOS inhibition with L-NAME had no effect on basal or isoproterenol-stimulated glycerol in the obese group in skeletal muscle or in adipose tissue. In contrast, L-NAME augmented the lipolytic response in lean subjects in both tissues. Differences in eNOS and iNOS mRNA expression at the adipose tissue level may have a limited effect on lipolysis and tissue perfusion. The lower resting lipolysis in adipose tissue of obese compared with nonobese subjects cannot be explained by a tonic nitric oxide effect.