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11-β-羟基类固醇脱氢酶1型在3T3-L1细胞分化及饮食诱导肥胖大鼠中的作用。

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

作者信息

Liu Yun, Sun Wen-Lan, Sun Yan, Hu Gang, Ding Guo-Xian

机构信息

Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.

出版信息

Acta Pharmacol Sin. 2006 May;27(5):588-96. doi: 10.1111/j.1745-7254.2006.00316.x.

Abstract

AIM

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

METHODS

Protein expression of 11beta-HSD1 in the process of 3T3-L1 cell differentiation and in various tissues of the rats were detected by Western blot analysis; expression of 11beta-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 11beta-HSD1, especially in the late stages of 3T3-L1 cell differentiation, was detected. The relative mRNA levels of 11beta-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 11beta-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

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

摘要

目的

观察11-β-羟类固醇脱氢酶1型(11β-HSD1)在体外前脂肪细胞分化及饮食诱导肥胖(DIO)大鼠中的作用。

方法

采用蛋白质免疫印迹法检测3T3-L1细胞分化过程及大鼠各组织中11β-HSD1的蛋白表达;采用实时定量PCR检测11β-HSD1 mRNA、糖皮质激素受体(GR)及其他前脂肪细胞分化标志物基因的表达。

结果

刺激后3T3-L1细胞内脂滴积聚并增多。检测到11β-HSD1蛋白水平显著升高,尤其在3T3-L1细胞分化后期。分化过程中,11β-HSD1、GR及细胞分化标志物脂蛋白脂肪酶(LPL)、脂肪细胞脂肪酸结合蛋白(aP2)和脂肪酸合酶(FAS)的相对mRNA水平上调,而前脂肪细胞因子-1(Pref-1)下调。在DIO大鼠中,体重、内脏脂肪质量指数及11β-HSD1蛋白表达增加,尤其在脂肪组织、脑和肌肉中。发现DIO大鼠血清胰岛素、甘油三酯、总胆固醇和低密度脂蛋白胆固醇升高,但血糖或肿瘤坏死因子-α水平无明显变化。

结论

11β-HSD1可能促进前脂肪细胞分化,并可能参与肥胖的发生发展。

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