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Dissociation between Adipose Nitric Oxide Synthase Expression and Tissue Metabolism

Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, D-13125 Berlin, Germany

Address all correspondence and requests for reprints to: Jens Jordan, M.D., Franz-Volhard Clinical Research Center, Charité Campus Buch, Wiltbergstrasse 50, 13125 Berlin, Germany. E-mail: jens.jordan{at}charite.de.

Context: Nitric oxide synthase (NOS) expression in adipose tissue is increased in obese subjects. The functional relevance is not known.

Objective: The objective was to compare adipose tissue metabolism between obese men with greater or lower adipose endothelial NOS (eNOS) or inducible NOS (iNOS) expression.

Design: The design was an open-labeled prospective study.

Setting: The study took place at an academic clinical research center.

Patients: The patients included 14 obese (32 ± 0.6 kg/m²) and eight normal-weight (23 ± 2 kg/m²) healthy men.

Intervention: Microdialysis catheters in abdominal sc adipose tissue and in vastus lateralis were perfused with N--nitro-L-arginine methyl ester (L-NAME) or N--nitro-D-arginine methyl ester (D-NAME). Then, incremental isoproterenol concentrations were added to the perfusate.

Main Outcome Measures: Microdialysate glycerol was the main outcome measure.

Results: 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.

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 with nonobese subjects cannot be explained by a tonic nitric oxide effect.