11β‐Hydroxysteroid Dehydrogenase Type 1 mRNA is Increased in Both Visceral and Subcutaneous Adipose Tissue of Obese Patients

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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.

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