Acta Pharmacologica Sinica 2006 May; 27 (5): 588-596; doi: 10.1111/j.1745-7254.2006.00316.x

Aim: To observe the roles of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in in vitro preadipocyte differentiation and in rats with diet-induced obesity (DIO).

Methods: Protein expression of 11β-HSD1 in the process of 3T3-L1 cell differentiation and in various tissues of the rats were detected by Western blot analysis; expression of 11β-HSD1 mRNA and glucocorticoid receptor (GR) and other marker genes of preadipocyte differentiation were detected by using real-time PCR.

Results: Lipid droplets in 3T3-L1 cells accumulated and increased after stimulation. A dramatically elevated protein level of 11β-HSD1, especially in the late stages of 3T3-L1 cell differentiation, was detected. The relative mRNA levels of 11β-HSD1, GR and cell differentiation markers LPL, aP2, and FAS were upregulated, and Pref-1 was downregulated during the differentiation. In DIO rats, bodyweight, visceral adipose mass index and the protein expression of 11β-HSD1 increased, especially in adipose tissue, brain and muscles. Serum insulin, triglyceride, total cholesterol and low-density lipoprotein cholesterol were found to be increased in DIO rats, but without any obvious changes in blood glucose or tumor necrosis factor-α levels.

Conclusion: 11β-HSD1 may promote preadipocyte differentiation, and may be involved in the development of obesity.

Keywords: 11-beta-hydroxysteroid dehydrogenase type 1; glucocorticoids; adipocytes; cell differentia-tion; obesity