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Keywords:

  • glucocorticoids;
  • local metabolism;
  • hexose-6-phosphate dehydrogenase;
  • human;
  • reverse transcriptase-polymerase chain reaction

Abstract

Objective: Data from rodents provide evidence for a causal role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) in the development of obesity and its complications. In humans, 11β-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11β-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11β-HSD-1 in human visceral adipose tissue (VAT), although VAT is the major predictor for insulin resistance and the metabolic syndrome.

Research Methods and Procedures: 11β-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11β-HSD-1 oxoreductase activity) mRNA levels were measured using real-time quantitative reverse transcriptase-polymerase chain reaction in abdominal SAT and VAT biopsies obtained from 10 normal-weight and 12 obese women. Adiponectin mRNA was used as an internal control.

Results: 11β-HSD-1 mRNA concentrations were significantly increased in both SAT and VAT of obese patients (720% and 450% of controls, respectively; p < 0.05) and correlated with hexose-6-phosphate dehydrogenase mRNA levels. The level of VAT 11β-HSD-1 mRNA correlated with anthropometric parameters: BMI (r = 0.41, p = 0.05), waist circumference (r = 0.44, p = 0.04), abdominal sagittal diameter (r = 0.51, p = 0.02), and percentage fat (r = 0.51, p = 0.02).

Discussion: Our results demonstrate for the first time that 11β-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11β-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11β-HSD-1 inhibitors.