Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline.
Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline.
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DOI：
10.3390/ijms23010001
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发表时间：
2021-12-21
影响因子：
5.6
通讯作者：
Kaestner KH
中科院分区：
文献类型：
--
作者：
Costa-Júnior JM;Ferreira SM;Kurauti MA;Bernstein DL;Ruano EG;Kameswaran V;Schug J;Freitas-Dias R;Zoppi CC;Boschero AC;Oliveira CAM;Santos GJ;Carneiro EM;Kaestner KH
背景/目的：表观遗传调控被认为是健康与疾病（DOHAD）假说的主要分子机制。以前的研究调查了父亲运动对后代代谢健康的作用，但没有控制训练的数量和强度，也没有控制对运动的适应可能产生的影响，并且在父母运动对下一代的好处方面产生了相互矛盾的结果。我们采用精确调节的运动方案来研究改善代谢健康的跨代遗传。方法：我们对雄性小鼠进行控制良好的运动训练，以研究父亲运动对其成年后代葡萄糖耐量和胰岛素敏感性的影响。为了研究表观遗传的分子机制，我们测定了后代和父亲精子骨骼肌的染色质标记。结果：经过训练的雄性小鼠的后代表现出改善的葡萄糖稳态和胰岛素敏感性。父本运动可调节后代骨骼肌中PI3Kca和印迹H19/Igf2位点的DNA甲基化谱，从而影响其基因表达。值得注意的是，在祖精子中存在类似的PI3Kca、H19和Igf2基因的DNA甲基化谱，这表明在生殖细胞发育过程中发生的运动诱导的表观遗传变化有助于跨代传播。结论：父本运动可作为促进后代代谢健康的一种策略，其益处可跨代遗传。
Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.
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影响因子：
8.2
作者：
Ling, C.;Del Guerra, S.;Lupi, R.;Ronn, T.;Granhall, C.;Luthman, H.;Masiello, P.;Marchetti, P.;Groop, L.;Del Prato, S.
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64.5
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Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
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影响因子：
29
作者：
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通讯作者：
Zierath, Juleen R.
影响因子：
3.5
作者：
Costa Junior, Jose M.;Rosa, Morgana R.;Carneiro, Everardo M.
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Carneiro, Everardo M.