DNA Methylation And Gene Expression Of PGC-1αlpha In Skeletal Muscle Of IUGR Rats With Catch-up Growth

Background and Objective:Catch-up growth IUGR (CG-IUGR) individual is prone to insulin resistance. Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-lalpha) is a hub of nutrition and energy metabolism. We hypothesize that the DNA methylation and gene expression of PGC-lalpha in skeletal muscle play a role in the mechanism of insulin resistance of CG-IUGR rats.Methods:A CG-IUGR rat model was established through maternal nutritional restriction and reduction of litter size from postnatal day1. The8-week rats were sacrificed for hind-limb skeletal musle tissue, and the RNA, protein and DNA were extracted. Realtime quantitative PCR and western blot were used to determine the expression level of PGC-1α; After bisulfite treated, DNA was used in PCR to amplify the sequence of PGC-la promoter, the methylation level of the specifi CpG sites in PGC-lalpha promoter were analyzed by pyrosequencing.Results:CG-IUGR rats showed increase in methylation level of specific sites-787and-803in PGC-1alpha promoter (p<0.01), and decrease in the PGC-lalpha expression compare with control (p<0.05). The BMI was positively correlated with methylation level of specific sites in PGC-lalpha promoter (p<0.01), while inversely correlated with the abundance of PGC-lalpha mRNA (p<0.05). However, the PGC-lalpha mRNA was not correlated with methylation level of PGC-lalpha promoter (p>0.05).Conclusion:The gene expression and DNA methylation of PGC-1alpha were changed in the muscle of CG-IUGR rats. The malnutritional intrauterine environment and well-fed postnatal environment probably introduce the change of PGC-1alpha together, programming insulin resistance phenotype of CG-IUGR rats.