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


METHODS
11beta-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11beta-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
11beta-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 11beta-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).


CONCLUSIONS
Our results demonstrate for the first time that 11beta-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11beta-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11beta-HSD-1 inhibitors.
Desbriere
Raoul
R
Service de Gynécologie/Obstétrique, CHU Nord, Marseille, France.
Vuaroqueaux
Vincent
V
Achard
Vincent
V
Boullu-Ciocca
Sandrine
S
Labuhn
Martin
M
Dutour
Anne
A
Grino
Michel
M
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002237:Carbohydrate Dehydrogenases / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000201:enzymology / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D049629:Waist-Hip Ratio
D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1