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[结节性硬化症1基因启动子甲基化率、食物诱导肥胖大鼠下丘脑雷帕霉素靶蛋白表达]

[Tsc1 promoter methylation rate, mTOR expression in food-induced obese rat hypothalamus].

作者信息

Zhang Lin, Li Ke, He Hong, Hu Mao-qing

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2015 Jan;46(1):47-50.

PMID:25807795
Abstract

OBJECTIVE

To investigate the methylation rate of tuberous sclerosis complex 1 (Tsc1) promoter and expression of mammalian target of rapamycin (mTOR) in food-induced rat hypothalamus.

METHODS

16 male SD rats were divided into high fat diet induced group (8 rats) and normal control group (8 rats) feeding for 12 weeks. Body mass, mass of celiac fat, celiac fat/body mass were measured. Methylation of Tsc1 promoter, mRNA and protein expression of mTOR were detected by bisulfite sequencing method, RT-PCR and Western blot, respectively.

RESULTS

Mass of celiac fat, celiac fat/body mass were higher in food-induced rat than that in control group. There were 11 methylation sites in SD rat hypothalamus. Obese group has significantly higher methylation rates (94.50% +/- 4.66%) than that of control group (86.60% +/- 3.49%) (P<0.002). The mRNA and protein expression of mTOR were noted lower in control group than in obese group (P<0.05).

CONCLUSION

The increased methylation rate of Tsc1 promoter in food-induced rat hypothalamus and up-regulated expression of mTOR, downstream gene of Tsc1 may promote the obesity.

摘要

目的

研究食物诱导的大鼠下丘脑结节性硬化复合物1(Tsc1)启动子的甲基化率及雷帕霉素靶蛋白(mTOR)的表达。

方法

将16只雄性SD大鼠分为高脂饮食诱导组(8只)和正常对照组(8只),喂养12周。测量体重、腹腔脂肪量、腹腔脂肪/体重。分别采用亚硫酸氢盐测序法、RT-PCR和蛋白质免疫印迹法检测Tsc1启动子的甲基化、mTOR的mRNA和蛋白表达。

结果

食物诱导的大鼠腹腔脂肪量、腹腔脂肪/体重高于对照组。SD大鼠下丘脑有11个甲基化位点。肥胖组甲基化率(94.50%±4.66%)显著高于对照组(86.60%±3.49%)(P<0.002)。对照组mTOR的mRNA和蛋白表达低于肥胖组(P<0.05)。

结论

食物诱导的大鼠下丘脑Tsc1启动子甲基化率增加,Tsc1下游基因mTOR表达上调,可能促进肥胖。

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