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Nitric oxide (NO) is involved in adipose tissue biology by influencing adipogenesis, insulin-stimulated glucose uptake, and lipolysis. The enzymes responsible for NO formation in adipose cells are endothelial NO synthase (eNOS) and inducible NO synthase (iNOS), whereas neuronal NO synthase (bNOS) is not expressed in adipocytes. We characterized the expression pattern and the influence of adipogenesis, obesity, and weight loss on genes belonging to the NO system in human subcutaneous adipose cells by combining in vivo and in vitro studies. Expression of most of the genes known to belong to the NO system (eNOS, iNOS, subunits of the soluble guanylate cyclase, and both genes encoding cGMP-dependent protein kinases) in human adipose tissue and isolated human adipocytes was detected. In vitro adipogenic differentiation increased the expression level of iNOS significantly, whereas eNOS expression levels were not influenced. The genes encoding eNOS, iNOS, and cGMP-dependent protein kinase 1 were expressed at higher levels in obese women. Expression of these genes, however, was not influenced by 5% weight loss. Insulin and angiotensin II (Ang II) increased NO production by human preadipocytes in vitro. Increased eNOS and iNOS expression in adipocytes and local effects of insulin and Ang II may increase adipose tissue production of NO in obesity.

Objectives: The activity of adipose 11β‐hydroxysteroid dehydrogenase (11β‐HSD) 1 is increased in obese subjects, and animal data suggest that increased cortisol formation in adipose tissue contributes to the development of the metabolic syndrome. The aim of this study was to determine whether up‐regulation of human adipose 11β‐HSD1 in obesity can also be found at the gene expression level. Research Methods and Procedures: 11β‐HSDgene expression in subcutaneous adipose tissue biopsies of 70 postmenopausal women was studied by real‐time reverse‐transcription polymerase chain reaction. The influence of weight reduction and in vitro effects of several modulators of adipocyte gene expression on 11β‐HSDgenes in human adipocytes were also studied. Results: The 11β‐HSD1gene was highly expressed in human adipose tissue. 11β‐HSD2mRNA was also detectable at lower levels. Adipose 11β‐HSD1gene expression was increased by two‐fold and was positively correlated with waist circumference and homeostasis model assessment index of insulin resistance. 11β‐HSD2gene expression was reduced by half in obese women. Weight reduction did not change gene expression levels of 11β‐HSD1or 11β‐HSD2. Cortisol increased 11β‐HSD1gene expression in isolated human adipocytes in vitro, whereas estradiol, triiodothyronine, angiotensin II, and pioglitazone had no influence. Discussion: Our data suggest that increased expression of the 11β‐HSD1gene is associated with metabolic abnormalities in obese women and that increased expression of this gene may contribute to the previously reported increased local conversion of cortisone to cortisol in adipose tissue of obese individuals.