Exercise Prevents Maternal High-Fat Diet–Induced Hypermethylation of the Pgc-1α Gene and Age-Dependent Metabolic Dysfunction in the Offspring

  1. Zhen Yan1,2,3,4,5
  1. 1Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA
  2. 2Center for Skeletal Muscle Research at the Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA
  3. 3Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore
  4. 4Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA
  5. 5Department of Molecular Physiology & Biological Physics, University of Virginia School of Medicine, Charlottesville, VA
  1. Corresponding authors: Jessica J. Connelly, jessica.connelly{at}, and Zhen Yan, zhen.yan{at}


Abnormal conditions during early development adversely affect later health. We investigated whether maternal exercise could protect offspring from adverse effects of a maternal high-fat diet (HFD) with a focus on the metabolic outcomes and epigenetic regulation of the metabolic master regulator, peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α). Female C57BL/6 mice were exposed to normal chow, an HFD, or an HFD with voluntary wheel exercise for 6 weeks before and throughout pregnancy. Methylation of the Pgc-1α promoter at CpG site −260 and expression of Pgc-1α mRNA were assessed in skeletal muscle from neonatal and 12-month-old offspring, and glucose and insulin tolerance tests were performed in the female offspring at 6, 9, and 12 months. Hypermethylation of the Pgc-1α promoter caused by a maternal HFD was detected at birth and was maintained until 12 months of age with a trend of reduced expression of Pgc-1α mRNA (P = 0.065) and its target genes. Maternal exercise prevented maternal HFD-induced Pgc-1α hypermethylation and enhanced Pgc-1α and its target gene expression, concurrent with amelioration of age-associated metabolic dysfunction at 9 months of age in the offspring. Therefore, maternal exercise is a powerful lifestyle intervention for preventing maternal HFD-induced epigenetic and metabolic dysregulation in the offspring.

  • Received October 18, 2013.
  • Accepted December 30, 2013.

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  1. Diabetes vol. 63 no. 5 1605-1611
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