Maternal protein restriction in rats leads to reduced PGC-1α expression via altered DNA methylation in skeletal muscle

Zeng,Yu; Gu,Pingqing; Liu,Kangsheng; Huang,Peilin

doi:10.3892/mmr.2012.1134

Maternal protein restriction in rats leads to reduced PGC-1α expression via altered DNA methylation in skeletal muscle

Authors:
- Yu Zeng
- Pingqing Gu
- Kangsheng Liu
- Peilin Huang
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Affiliations: School of Medicine, Southeast University, Jiangsu 210096, P.R. China, State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Nanjing Maternity and Child Healthcare Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China, Department of Pathology, Medical College, Southeast University, Jiangsu 210096, P.R. China
Published online on: October 19, 2012 https://doi.org/10.3892/mmr.2012.1134
Pages: 306-312

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Abstract

Intrauterine growth retardation (IUGR) is thought to program insulin resistance, type 2 diabetes and other metabolic diseases in later life. Skeletal muscle is an important tissue involved in regulating the metabolism. We therefore hypothesized that the regulation of glucose- and lipid-related genes in skeletal muscle may contribute to metabolic changes in rats with IUGR. In this study, IUGR rats were bred from pregnant rats fed a protein-restricted (PR) diet. Insulin resistance (IR)-related metabolic parameters and the expression of key regulatory IR genes such as peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and glucose transporter 4 (GLUT4) were measured in skeletal muscle from 18-month-old female IUGR rats. The methylation status of promoters of PGC-1α and GLUT4 were assessed in the same tissues. During the aging process, IUGR rats exhibited catch-up growth and obesity. In old age, they showed impaired glucose tolerance demonstrated by high glucose and insulin AUC (area under the curve) values. The expression of glucose transporter 4 (GLUT4) and PGC-1α in skeletal muscle was significantly reduced in IUGR rats. Mean CpG island methylation in the PGC-1α promoter sequence was significantly increased. These results suggest that a PR diet during gestation may induce epigenetic changes, such as DNA methylation, in the promoters of specific genes. The changes may affect gene expression and account for the metabolic alterations in female rats with IUGR.

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