Down-regulation of PPAR-γexpression by p300-mediated histone acetyla-tion induces glucose-lipid metabolism disorder in cardiomyocytes of GDM offspring mice
10.3969/j.issn.1000-4718.2017.12.017
- VernacularTitle:p300介导组蛋白乙酰化修饰下调PPAR-γ致妊娠期 糖尿病小鼠子代心肌细胞糖脂代谢紊乱
- Author:
Wei ZHANG
1
;
Cong CHEN
Author Information
1. 成都市第一人民医院儿科
- Keywords:
Gestational diabetes mellitus;
p300;
Peroxisome proliferator-activated receptor-γ;
Cardiomyo-cytes;
Glucose-lipid metabolism disorder
- From:
Chinese Journal of Pathophysiology
2017;33(12):2222-2226
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of gestational diabetes mellitus ( GDM) on glucose-lipid metabolism in the offspring mice and the underlying mechanisms .METHODS:Wild-type female mice were intraperitoneally injected with streptozotocin at 30 mg/kg in the second trimester of pregnancy to establish GDM model .Normal saline was used as control.F1 offspring mice were fed for 8 weeks after birth.The blood glucose and lipid levels were detected randomly .The mRNA levels of p300 and p300/CBP-associated factor ( PCAF) were detected by qPCR .The expression of peroxisome pro-liferator-activated receptor-γ( PPAR-γ) , glucose transporter typer 4 ( GLUT-4 ) and medium-chain acyl-CoA dehydroge-nase ( MCAD) at mRNA and protein levels was determined by qPCR and Western blot .ChIP-qPCR was employed to ana-lyze the binding status of p 300 with the promoter of PPAR-γand the acetylation level of histone H 3 in the promoter region of PPAR-γ.RESULTS:Blood glucose and total cholesterol levels were significant increased in the offspring mice ( P<0.05).The expression levels of p300, PPAR-γ, GLUT-4 and MCAD were decreased compared with the control group (P<0.05).Binding affinity of p300 with the promoter of PPAR-γwas reduced (P<0.05).The level of acetylated his-tone H3 in the promoter region of PPAR-γwas decreased significantly ( P<0.05) .CONCLUSION:Regulation of PPAR-γexpression by p300 may induce glucose-lipid metabolism disorder in the cardiomyocytes of GDM offspring mice .
