Down-regulation of PPAR-γexpression by p300-mediated histone acetyla-tion induces glucose-lipid metabolism disorder in cardiomyocytes of GDM offspring mice / 中国病理生理杂志

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 .