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

Abstract

DESBRIERE, RAOUL, VINCENT VUAROQUEAUX, VINCENT ACHARD, SANDRINE BOULLU-CIOCCA, MARTIN LABUHN, ANNE DUTOUR, AND MICHEL GRINO. Increased expression of 11␤-hydroxysteroid dehydrogenase type 1 mRNA in both visceral and subcutaneous adipose tissue of obese patients. Obesity. 2006;14:794 -798. Objective: Data from rodents provide evidence for a causal role of 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) in the development of obesity and its complications. In humans, 11␤-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11␤-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11␤-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: 11␤-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11␤-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: 11␤-HSD-1 mRNA concentrations were significantly increased in both SAT and VAT of obese patients (720% and 450% of controls, respectively; p Ͻ 0.05) and correlated with hexose-6-phosphate dehydrogenase mRNA levels. The level of VAT 11␤-HSD-1 mRNA correlated with anthropometric parameters: BMI (r ϭ 0.41, p ϭ 0.05), waist circumference (r ϭ 0.44, p ϭ 0.04), abdominal sagittal diameter (r ϭ 0.51, p ϭ 0.02), and percentage fat (r ϭ 0.51, p ϭ 0.02). Discussion: Our results demonstrate for the first time that 11␤-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11␤-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11␤-HSD-1 inhibitors.

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

“…Recent studies suggest that in some cases 11 -HSD1 mRNA levels are also increased in visceral omental adipose tissue of obese women and are a strong predictor of fat cell size in this visceral depot (Desbriere et al, 2006, Michailidou et al, 2007, Paulsen et al, 2007. 11 -HSD1 might impact differentially on the pathophysiology of distinct fat depots in obesity.…”

Neuroendocrine mechanisms in insulin resistance

“…Cortisone reenters the circulation and is available for conversion to cortisol, in tissues with high 11β-HSD-1 expression, in particular adipose tissue and liver. It is of interest to explore whether there are differences in expression of 11β-HSD-1 in visceral and subcutaneous adipose tissue, but there are reports suggesting a higher expression in visceral tissue as well as no difference (53)(54)(55). Nonetheless, it seems that both depots display elevated 11β-HSD-1 expression in obesity (54,55).…”

“…It is of interest to explore whether there are differences in expression of 11β-HSD-1 in visceral and subcutaneous adipose tissue, but there are reports suggesting a higher expression in visceral tissue as well as no difference (53)(54)(55). Nonetheless, it seems that both depots display elevated 11β-HSD-1 expression in obesity (54,55). Genetic animal models give support for the link between adipose tissue 11β-HSD-1 activity and metabolic phenotype (56,57).…”

Glucocorticoids and Cardiovascular Disease

“…11b-HSD2 activity is deficient in a substantial minority of patients with essential hypertension (46, 47) and predicts salt sensitivity of blood pressure (48). 11b-HSD1 activity is increased in the adipose tissue of obese people (40, [49][50][51][52][53][54][55][56][57][58] and predicts the severity of associated metabolic complications of obesity (52,59,60). Inhibitors of 11b-HSD1 are in development for the treatment of type 2 diabetes and other features of metabolic syndrome, and have shown considerable promise in animal models (61-65) (see below).…”