Acta Pharmacologica Sinica 2007 August; 28 (8): 1198-1204; doi: 10.1111/j.1745-7254.2007.00602.x

Aim: To investigate the relationship between 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), a potential link between obesity and type 2 diabetes, and preadipocyte differentiation.

Methods: Mouse 11beta-HSD1 siRNA plasmids were transfected into 3T3-L1 preadipocytes (a cell line derived from mouse Swiss3T3 cells that were isolated from mouse embryo), for examination of the effect of targeted 11beta-HSD1 inhibition on differentiation of 3T3-L1 cells. Differentiation was stimulated with 3-isobutyl-1-methyxanthine, insulin, and dexamethasone. The transcription level of the genes was detected by real-time PCR.

Results: Lipid accumulation was significantly inhibited in cells transfected with mouse 11beta-HSD1 siRNA compared with non-transfected 3T3-L1 cells. Fewer lipid droplets were detected in the transfected cells both prior to stimulation and after stimulation with differentiation-inducing reagents. The expression of adipocyte differentiation-associated markers such as lipoprotein lipase and fatty acid synthetase were downregulated in the transfected cells. Similarly, the expression of preadipocyte factor-1, an inhibitor of adipocyte differentiation, was downregulated upon stimulation of differentiation and had no changes in the transfected cells.

Conclusion: 11 beta-HSD1 can promote preadipocyte differentiation. Based on this, we propose that 11 beta-HSD1 may be an important candidate mediator of obesity and obesity-induced insulin resistance.

Keywords: 11 beta-hydroxysteroid dehydrogenase type 1; siRNA; 3T3-L1; cell differentiation; obesity