TY - JOUR

T1 - Exercise during pregnancy mitigates negative effects of parental obesity on metabolic function in adult mouse offspring

AU - Laker, Rhianna Che C

AU - Altıntaş, Ali

AU - Lillard, Travis S

AU - Zhang, Mei

AU - Connelly, Jessica J

AU - Sabik, Olivia L

AU - Onengut, Suna

AU - Rich, Stephen S

AU - Farber, Charles R

AU - Barrès, Romain

AU - Yan, Zhen

PY - 2021

Y1 - 2021

N2 - 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 as well as targeted DNA methylation analysis of the peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) promoter in the both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9 months of age, while 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 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.

AB - 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 as well as targeted DNA methylation analysis of the peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) promoter in the both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9 months of age, while 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 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.

U2 - 10.1152/japplphysiol.00641.2020

DO - 10.1152/japplphysiol.00641.2020

M3 - Journal article

C2 - 33332990

VL - 130

SP - 605

EP - 616

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 3

ER -