Dissociation between adipose nitric oxide synthase expression and tissue metabolism

J Clin Endocrinol Metab. 2007 Jul;92(7):2706-11. doi: 10.1210/jc.2007-0234. Epub 2007 Apr 24.

Abstract

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-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.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / enzymology*
  • Adrenergic beta-Agonists / administration & dosage
  • Adult
  • Body Weight
  • Enzyme Inhibitors / administration & dosage
  • Gene Expression Regulation, Enzymologic
  • Glycerol / metabolism
  • Humans
  • Isoproterenol / administration & dosage
  • Lipolysis / physiology
  • Male
  • Microdialysis
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide Synthase Type II / genetics*
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism*
  • Obesity / metabolism*
  • Prospective Studies

Substances

  • Adrenergic beta-Agonists
  • Enzyme Inhibitors
  • NOS3 protein, human
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Isoproterenol
  • Glycerol
  • NG-Nitroarginine Methyl Ester