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.
J Appl Physiol (1985). 2021 Mar 1;130(3):605-616. doi: 10.1152/japplphysiol.00641.2020. Epub 2020 Dec 17.
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 () 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 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. 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.
父母的健康状况会影响胚胎发育和后代对疾病的易感性。我们研究了母体在妊娠期是否可以自愿跑步，以保护后代免受母体或父体高脂肪饮食（HF）的不利影响。我们对雌性后代骨骼肌进行了转录组和全基因组 DNA 甲基化分析，并对雄性和雌性成年后代的过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）启动子进行了靶向 DNA 甲基化分析。母体 HF 在雄性后代 9 个月大时导致代谢稳态受损，而雄性和雌性后代都受到父体 HF 的负面影响。母体在妊娠期的运动完全减轻了这些代谢损伤。来自肥胖雄性或雌性父母的成年雌性后代的骨骼肌转录谱富含调节炎症和免疫反应的基因，而母体运动导致与来自正常饮食（NC）喂养父母的后代相似的转录谱。母体 HF 但不是父体 HF 导致 CpG-260 处的 启动子超甲基化，而母体运动则消除了这种超甲基化。这些发现表明，母体和父体 HF 对后代的代谢结果产生负面影响，可能通过不同的表观遗传机制，而妊娠期母体运动则减轻了这种负面影响。母体或父体肥胖会导致成年后代代谢受损。母体在妊娠期的运动可以完全减轻代谢损伤。母体肥胖，但不是父体肥胖，会导致 CpG-260 处的 PGC-1α 启动子超甲基化，而母体运动可以消除这种超甲基化。
