Dissociation between adipose nitric oxide synthase expression and tissue metabolism

Context: Nitric oxide synthase (NOS) expression in adipose tissue is increased in obese subjects. The functional relevance is not known. Objective: To compare adipose tissue metabolism between obese men with greater or lower adipose eNOS or iNOS expression. Design: Prospective, open-label. Setting: Academic clinical research center. Patients: 14 obese (32+/-0.6 kg/m(2)) and 8 normal weight (23+/-2 kg/m(2)) healthy men. Intervention: Perfusion of microdialysis catheters in abdominal subcutaneous adipose tissue and in vastus lateralis muscle with L-NAME or with D-NAME. Addition of incremental isoproterenol concentrations to the perfusate. Main outcome measures: Microdialysate glycerol. Results: Tissue perfusion and microdialysate glycerol concentrations at baseline and during isoproterenol stimulation were similar in obese men with high or with low eNOS or iNOS expression, both, during L-NAME and during 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. Conclusions: 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 to nonobese subjects cannot be explained by a tonic NO effect