University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
Department of Neonatal Medicine, University Hospital of Angers, Angers, France.
Sci Rep. 2017 Mar 14;7:44650. doi: 10.1038/srep44650.
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.
怀孕期间肥胖的患病率继续以惊人的速度增长。这令人担忧，因为除了对母亲健康的直接影响外，怀孕期间肥胖还通过非遗传机制对后代的长期健康产生不利影响。一个限制我们开发干预策略能力的主要知识差距是，我们缺乏对肥胖母亲体内介导这些表观遗传效应的因素的理解。我们使用了一种由母体饮食引起的肥胖的小鼠模型，以确定母体因素与后代胰岛素抵抗之间的预测相关性。母体高胰岛素血症（与母体体重和组成无关）与后代胰岛素抵抗强烈相关。为了验证因果关系，我们实施了一项运动干预措施，该措施改善了母体的胰岛素敏感性，而不改变母体的体重或组成。这种母体干预措施可防止胎盘脂质沉积过多和缺氧（与性别无关）以及雄性后代的胰岛素抵抗。我们的结论是，高胰岛素血症是一个关键的编程因素，因此是肥胖妊娠期间的一个重要干预靶点，并提出适度运动是改善肥胖母亲及其后代代谢结果的一种有前途的策略。
