Endocrine Abstracts (2006) 11 P757

11beta-hydroxysteroid dehydrogenase is an early and essential marker of human adipogenesis

IJ Bujalska1, LL Gatherocole1, JW Tomlinson1, C Darimont2 & PM Stewart1


1University of Birmingham, Birmingham, United Kingdom; 2Nestle Research Centre, Lausanne, Switzerland.


The prevalence of obesity and its association with many health complications have evoked a high interest in adipose tissue metabolism. In man, glucocorticoid (GC) excess increases fat mass and the risk of developing Metabolic Syndrome. The enzyme responsible for modifying intracellular GC concentrations in adipose tissue is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The aim of this study was to characterise the novel human preadipocyte cell line (Chub-S7) and explore the role of 11β-HSD1 in adipocyte differentiation. Chub-S7 cells were differentiated for up to 17 days in serum-free DMEM/F12 with insulin, PPARγ2 agonist and cortisol (F) and gene expression determined by real-time PCR. To study the effect of 11β-HSD1 on preadipocyte differentiation, cells were cultured in differentiation media containing 500 nM cortisone (E) (inactive GC) together with 1 μM glycyrrhetinic acid (GE). Adipogenesis was studied by measuring expression levels of differentiation markers including fatty acid binding protein 4 (FABP4) and glycerol 3 phosphate dehydrogenase (G3PDH) by real-time PCR. Proliferating Chub-S7 cells did not express 11β-HSD1, FABP4 or G3PDH. From day 1 of differentiation, a linear increase in 11β-HSD1 mRNA was observed (29.3-fold change on day 1 and 290.6 on day 9 vs day 0, P<0.001). mRNA expression paralleled oxo-reductase activity, E to F (0 day 1, 3.0 day 4 and 12.9 day 9, pmol/mg/h, P<0.001). FABP4 and G3PDH mRNA expression significantly increased from day 6 onwards. Co-differentiation with E increased FABP4 (637.8-fold on day 17 vs control, P<0.0001) and G3PDH mRNA expression (331.8-fold on day 17 vs control, P<0.0001). Co-incubation with GE significantly reduced the cortisone induced increases in adipogenic markers. We conclude that the increase in 11β-HSD1 mRNA expression and activity is essential for the early stages of adipogenesis. Specific 11β-HSD1 inhibitors may represent a novel approach for the treatment of obesity.

Article tools

My recent searches

No recent searches.