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.

中文翻译：

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孕期锻炼可减轻父母肥胖对成年小鼠后代代谢功能的负面影响

父母的健康会影响后代的胚胎发育和对疾病的易感性。我们调查了母亲在妊娠期间自愿跑步是否可以保护后代免受小鼠母亲或父亲高脂肪饮食 (HF) 的不利影响。我们对雌性后代骨骼肌进行转录组和全基因组 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 coactivator-1α (Pgc-1α) 启动子进行靶向 DNA 甲基化分析。母体 HF 导致 9 个月大的雄性后代代谢稳态受损，而雄性和雌性后代都受到父亲 HF 的负面影响。孕期的产妇运动完全减轻了这些代谢障碍。来自肥胖男性或女性父母的成年女性后代的骨骼肌转录谱富含调节炎症和免疫反应的基因，而母体运动导致的转录谱类似于正常食物喂养父母的后代。母体 HF，但不是父系 HF，导致 Pgc-1α 启动子在 CpG -260 处的高甲基化，这被母体运动消除。这些研究结果表明，母亲和父亲的 HF 可能通过不同的表观遗传机制对后代生命后期的代谢结果产生负面影响，而母亲在妊娠期间的锻炼可以减轻负面影响。而母体运动导致的转录谱类似于正常食物喂养父母的后代。母体 HF，但不是父系 HF，导致 Pgc-1α 启动子在 CpG -260 处的高甲基化，这被母体运动消除。这些研究结果表明，母亲和父亲的 HF 可能通过不同的表观遗传机制对后代生命后期的代谢结果产生负面影响，而母亲在妊娠期间的锻炼可以减轻负面影响。而母体运动导致的转录谱类似于正常食物喂养父母的后代。母体 HF，但不是父系 HF，导致 Pgc-1α 启动子在 CpG -260 处的高甲基化，这被母体运动消除。这些研究结果表明，母亲和父亲的 HF 可能通过不同的表观遗传机制对后代生命后期的代谢结果产生负面影响，而母亲在妊娠期间的锻炼可以减轻负面影响。