Exercise during pregnancy mitigates negative effects of parental obesity on metabolic function in adult mouse offspring
Exercise during pregnancy mitigates negative effects of parental obesity on metabolic function in adult mouse offspring
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DOI：
10.1152/japplphysiol.00641.2020
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发表时间：
2021-03-01
影响因子：
3.3
通讯作者：
Yan, Zhen
中科院分区：
文献类型：
--
作者：
Laker, Rhianna C.;Altintas, Ali;Yan, Zhen
父母的健康状况影响胚胎发育和后代对疾病的易感性。我们研究了妊娠期母亲自愿跑步是否可以保护后代免受母亲或父亲高脂肪饮食（HF）的不良影响。我们对雌性后代骨骼肌进行了转录组学和全基因组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体激活受体- γ辅助激活因子-1 α (Pgc-1 α)启动子进行了靶向DNA甲基化分析。母亲HF导致雄性后代在9月龄时代谢稳态受损，而父亲HF对雄性和雌性后代均有负面影响。母亲在怀孕期间的运动完全减轻了这些代谢障碍。来自肥胖雄性或雌性父母的雌性成年后代的骨骼肌转录谱富集了调节炎症和免疫反应的基因，而母亲运动导致的转录谱与正常食物（NC）喂养的父母的后代相似。母体HF导致Pgc-1 α启动子CpG-260位点的高甲基化，母体运动可消除该甲基化。这些发现表明，母亲和父亲的HF可能通过不同的表观遗传机制对后代以后的代谢结果产生负面影响，而母亲在怀孕期间的锻炼可以减轻这种负面影响。新的和值得注意的母亲或父亲肥胖导致小鼠成年后代的代谢障碍。妊娠期孕妇运动可以完全减轻代谢障碍。母亲肥胖，而不是父亲肥胖，导致Pgc-1 α启动子CpG-260的高甲基化，这可以通过母亲运动来消除。
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-gamma coactivator-1 alpha (Pgc-1 alpha) promoter in both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9mo 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-1 alpha 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-1 alpha promoter at CpG-260, which can be abolished by maternal exercise.