| Autor: |
Laker RC; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark., Altıntaş A; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark., Lillard TS; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia., Zhang M; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia., Connelly JJ; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia., Sabik OL; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Onengut S; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Rich SS; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Farber CR; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia., Barrès R; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark., Yan Z; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia.; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia. |
| Abstrakt: |
Parental health influences embryonic development and susceptibility to disease in the offspring. We investigated whether maternal voluntary running during gestation could protect the offspring from the adverse effects of maternal or paternal high-fat diet (HF) in mice. We performed transcriptomic and whole-genome DNA methylation analyses in female offspring skeletal muscle and targeted DNA methylation analysis of the peroxisome proliferator-activated receptor-γ coactivator-1α ( Pgc-1α ) promoter in both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9 mo of age, whereas both male and female offspring were negatively impacted by paternal HF. Maternal exercise during gestation completely mitigated these metabolic impairments. Female adult offspring from obese male or female parent had skeletal muscle transcriptional profiles enriched in genes regulating inflammation and immune responses, whereas maternal exercise resulted in a transcriptional profile similar to offspring from normal chow (NC)-fed parents. Maternal HF, but not paternal HF, resulted in hypermethylation of the Pgc-1α promoter at CpG-260, which was abolished by maternal exercise. These findings demonstrate the negative consequences of maternal and paternal HF for the offspring's metabolic outcomes later in life possibly through different epigenetic mechanisms, and maternal exercise during gestation mitigates the negative consequences. NEW & NOTEWORTHY Maternal or paternal obesity causes metabolic impairment in adult offspring in mice. Maternal exercise during gestation can completely mitigate metabolic impairment. Maternal obesity, but not paternal obesity, results in hypermethylation of the Pgc-1α promoter at CpG-260, which can be abolished by maternal exercise. |
