Exercise Prevents Maternal High-Fat Diet–Induced Hypermethylation of the Pgc-1α Gene and Age-Dependent Metabolic Dysfunction in the Offspring
- Rhianna C. Laker1,2,
- Travis S. Lillard1,
- Mitsuharu Okutsu1,2,3,
- Mei Zhang1,2,3,
- Kyle L. Hoehn2,4,
- Jessica J. Connelly1,5⇑ and
- Zhen Yan1,2,3,4,5⇑
- 1Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA
- 2Center for Skeletal Muscle Research at the Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA
- 3Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore
- 4Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA
- 5Department of Molecular Physiology & Biological Physics, University of Virginia School of Medicine, Charlottesville, VA
- Corresponding authors: Jessica J. Connelly, , and Zhen Yan, .
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.
- © 2014 by the American Diabetes Association.
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