代谢健康的代际遗传效应:基于母代妊娠期营养与运动的视角
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华南师范大学

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G804.2

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广州市重点研发项目


Intergenerational Effects on Metabolic Health: Insights from Maternal Exercise and Prenatal Nutrition
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South China Normal University

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Guangzhou Key Research and Development Program

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    摘要:

    随着我国儿童青少年代谢综合征的发病率逐渐升高,母亲妊娠期的营养状态和身体活动对子代代谢健康的影响逐渐成为研究热点。研究表明,妊娠期母亲不良饮食模式通过破坏胎盘功能稳态、影响宫内胎儿发育环境、调控胎儿代谢器官发育等作用途径,显著增加子代代谢性疾病的发生风险;然而,妊娠期规律的身体活动可通过改善母体代谢稳态、优化胎盘结构和功能、调控表观遗传修饰等途径,有效阻断代谢性疾病的垂直传播的潜在途径。基于此,本文探讨了母亲妊娠期营养与运动对子代代谢健康的潜在交互作用以及性别特异性效应,并深入探究了代谢“重编程”代际调控网络的复杂性,旨在为改善我国日益严峻的儿童青少年代谢障碍提供代际研究视角,并为优化妊娠期代谢健康管理策略提供理论依据。

    Abstract:

    With the increasing prevalence of overweight and obesity among children and adolescents in China, pediatric metabolic syndrome has emerged as a significant public health challenge. The Developmental Origins of Health and Disease (DOHaD) theory underscores the critical influence of early environmental factors on lifelong metabolic health. Consequently, maternal nutritional status and physical activity during pregnancy have become key modifiable factors that have attracted considerable attention in recent years. Research indicates exposure to a maternal high-fat diet (HFD) during pregnancy has long-term effects on offspring health, which may be transmitted through placental transit disorder, inflammation, and oxidative stress. Similarly, a high-protein diet (HPD) during pregnancy exhibits a dose- and time-dependent biphasic effect: excessive intake may lead to fetal growth restriction and an increased risk of preterm birth, whereas moderate supplementation may instead reduce the susceptibility of offspring to obesity. Interestingly, caloric restriction (CR) during pregnancy presents a double-edged sword: while it may impair the development of metabolic organs in offspring, moderate CR in metabolically compromised mothers can ameliorate maternal metabolic dysfunction and reprogram oocyte DNA methylation, significantly lowering the risk of metabolic disorders in offspring. Notably, metabolic abnormalities induced by a low-protein diet (LPD) during pregnancy demonstrate lifecycle-accumulative effects and transgenerational inheritance, with offspring exhibiting obesity phenotypes during weaning, insulin resistance in adulthood, and hepatic decompensation in old age, mediated through oocyte epigenetic reprogramming. Additionally, maintaining an optimal micronutrient balance is crucial for the metabolic homeostasis of offspring, as both deficiency and excess can lead to detrimental outcomes. Maternal exercise has been established as a safe and effective non-pharmacological intervention that confers multigenerational metabolic benefits through diverse biological pathways. Maternal metabolic dysregulation represents a critical determinant of offspring metabolic disorders. Regular exercise during gestation exerts protective effects by attenuating maternal systemic inflammation and reducing the incidence of pregnancy-related complications, thereby effectively mitigating fetal overgrowth and metabolic dysfunction. This dual benefit for both mother and offspring underscores the pivotal role of gestational physical activity in promoting long-term metabolic health. The placenta, serving as the exclusive interface for maternal-fetal communication, mediates exercise-induced metabolic programming through enhanced secretion of key regulatory factors (including SOD3, Apelin, ADPN, and Irisin) and promotes the development of vascular networks, collectively optimizing nutrient transport efficiency. The intrauterine period represents a crucial window for epigenetic reprogramming, during which maternal exercise modulates DNA methylation patterns of critical metabolic genes (e.g., Ppargc-1α, Prdm16, Klf4, and Slc23a2) in offspring, thereby enhancing their capacity to resist metabolic disorders. Notably, the regulatory effects of maternal exercise extend beyond the gestational period. Postnatally, exercise-induced modifications in the bioactive components of breast milk and gut microbiota composition contribute to the sustained maintenance of metabolic homeostasis in offspring, establishing a continuum of metabolic protection from prenatal to postnatal stages. This review explores the potential of maternal combined nutrition-exercise interventions, suggesting that such strategies may synergistically enhance transgenerational health benefits through interactions within the metabolic-epigenetic network, thereby outperforming single interventions. Additionally, it examines current research limitations, including controversies surrounding transgenerational mechanisms, sex-specific responses, and undefined dynamic thresholds, while providing directions for future investigations. These findings pave the way for a theoretical foundation for early-life health interventions, potentially offering a more effective strategy for combatting intergenerational metabolic disorders.

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李婕,石海旺,段 锐.代谢健康的代际遗传效应:基于母代妊娠期营养与运动的视角[J].生物化学与生物物理进展,,():

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  • 收稿日期:2025-03-30
  • 最后修改日期:2025-05-29
  • 接受日期:2025-05-30
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