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


Abnormal conditions during early development adversely impact later health. We investigated whether maternal exercise could protect the offspring from adverse effects of maternal HFD with a focus on the metabolic outcomes and epigenetic regulation of the metabolic master regulator, peroxisome proliferator activated receptor γ co-activator-1α (Pgc-1α). Female C57BL/6 mice were exposed to normal chow, HFD, or HFD with voluntary wheel exercise for 6 weeks prior to and throughout pregnancy. Methylation of the Pgc-1α promoter at CpG site -260 and Pgc-1α mRNA expression were assessed in skeletal muscle from neonatal and 12 month-old offspring, and glucose and insulin tolerance tests (GTT and ITT, respectively) were performed in the female offspring at 6, 9 and 12 months. Hypermethylation of the Pgc-1α promoter caused by maternal HFD was detected at birth, which was maintained to 12 month of age with a trend of reduced 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 in preventing maternal HFD-induced epigenetic and metabolic dysregulation in the offspring.

  • Received October 18, 2013.
  • Accepted December 29, 2013.

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