4.7 Article

Role of 11-beta-hydroxysteroid dehydrogenase type 1 in differentiation of 3T3-L1 cells and in rats with diet-induced obesity

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ACTA PHARMACOLOGICA SINICA
卷 27, 期 5, 页码 588-596

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ACTA PHARMACOLOGICA SINICA
DOI: 10.1111/j.1745-7254.2006.00316.x

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11-beta-hydroxysteroid dehydrogenase type 1; glucocorticoids; adipocytes; cell differentiation; obesity

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Aim: To observe the roles of 11-beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) in in vitro preadipocyte differentiation and in rats with diet-induced obesity (DIO). Methods: Protein expression of 11 beta-HSD1 in the process of 3T3-L1 cell differentiation and in various tissues of the rats were detected by Western blot analysis; expression of 11 beta-HSD1 mRNA and glucocorticoid receptor (GR) and other marker genes of preadipocyte differentiation were detected by using realtime PCR. Results: Lipid droplets in 3T3-L1 cells accumulated and increased after stimulation. A dramatically elevated protein level of 11 beta-HSD1, especially in the late stages of 3T3-L1 cell differentiation, was detected. The relative mRNA levels of 11 beta-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 11 beta-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-alpha levels. Conclusion: 11 beta-HSD1 may promote preadipocyte differentiation, and may be involved in the development of obesity.

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