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

Research output: Contribution to journalJournal articlepeer-review

  • Rhianna Che C Laker
  • Altintas, Ali
  • Travis S Lillard
  • Mei Zhang
  • Jessica J Connelly
  • Olivia L Sabik
  • Suna Onengut
  • Stephen S Rich
  • Charles R Farber
  • Barrès, Romain
  • Zhen Yan

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.

Original languageEnglish
JournalJournal of Applied Physiology
Issue number3
Pages (from-to)605-616
Publication statusPublished - 2021

ID: 253398247