Maternal Exercise Protects Offspring from Obesity and Insulin Resistance

描述(申请人提供)：宫内环境会影响发育中的胚胎的发育，不合适的环境会导致终止妊娠。然而，新出现的研究表明，更微妙的因素可能会影响后代的长期健康。例如，营养不良的孕妇生育的后代较小，成年后肥胖、糖尿病和心脏病的发病率较高。在这一点上，大多数发表的研究都集中在有害饮食或压力行为对后代造成的负面变化上。然而，在西方世界，母亲肥胖是一个日益严重的问题，流行病学研究现在指出，她们的后代存在代谢紊乱。为了积极主动，孕妇在怀孕期间自愿锻炼被选为一种潜在的短期干预措施，以改善后代的健康结果。运动母鼠所生后代的空腹循环血糖和胰岛素水平低于未运动母鼠所生的后代，并且葡萄糖代谢和胰岛素敏感性显著改善。因此，我们对这一建议的假设是，母亲在怀孕和哺乳期间自愿锻炼将改善血糖调节，并减少子代的肥胖和高血压。第一个目标是确定母亲自愿锻炼是否可以改善正常、标准饮食喂养的后代的胰岛素敏感性，并防止高热量饮食喂养的后代肥胖、胰岛素抵抗和高血压进展。第二个目的是希望通过增强胰岛素信号来阐明运动过的母鼠所生后代对胰岛素长期敏感的机制。第三个目标将确定母亲运动是否可以作为一种干预措施，以改善因母亲摄入高卡路里饮食或妊娠期糖尿病而导致的后代的病理结果。为了探索这些目标，雌鼠将被分成久坐不动或自愿锻炼的小组。运动水坝将在交配前以及怀孕和哺乳期间24小时使用转轮。在研究的任何部分，成熟的后代都不能使用跑轮。肥胖、葡萄糖和胰岛素耐量以及高血压将在喂养标准或高卡路里饮食的后代中进行监测。这些研究将提供有关母亲锻炼对后代健康可能产生的潜在积极影响的重要信息。肥胖、糖尿病和心血管疾病正处于流行水平，针对妊娠的干预可能是遏制这一趋势的有效方法。

DESCRIPTION (provided by applicant): The intrauterine environment affects the development of the growing embryo and an unsuitable environment can lead to termination of pregnancy. However, emerging research has shown that more subtle factors can potentially influence long-term health in the offspring. For instance, malnourished pregnant mothers produce smaller offspring that have a higher incidence of obesity, diabetes, and heart disease during adulthood. To this point, most published studies have focused on negative changes in offspring caused by detrimental diets or stressful behavior. However, in the Western world, maternal obesity is an ever-increasing problem and epidemiology studies are now pointing to metabolic derangements in their offspring. In an attempt to be pro-active, maternal voluntary exercise during pregnancy was chosen as a potential short-term intervention to improve health outcomes in offspring. Fasting circulating glucose and insulin levels were lower in offspring born to exercised dams compared to those born to non-exercised dams, and glucose disposal and insulin sensitivity were significantly improved. As a result, our hypothesis for this proposal is that maternal voluntary exercise during pregnancy and nursing will improve glucose regulation and decrease obesity and hypertension in offspring. The first aim is designed to determine whether maternal voluntary exercise can improve insulin sensitivity in offspring fed a normal, standard diet and protect against obesity, insulin resistance, and hypertension progression in high calorie diet-fed offspring. The second aim hopes to elucidate the mechanism for long-lasting insulin sensitivity in offspring born to exercised dams which is likely through enhanced insulin signaling. The third aim will determine whether maternal exercise can be used as an intervention to improve pathology outcomes in offspring resulting from maternal consumption of a high calorie diet or gestational diabetes mellitus. To explore these aims, female mice will be placed into sedentary or voluntary exercise groups. The exercise dams will have 24 hour access to running wheels before mating and throughout pregnancy and nursing. The maturing offspring will not have access to running wheels for any portion of the study. Obesity, glucose and insulin tolerance, and hypertension will be monitored in the offspring fed either standard or high calorie diet. These studies will provide important information on the potential positive impact maternal exercise can have on offspring health. Obesity, diabetes, and cardiovascular disease are at epidemic levels and interventions targeting gestation might be an efficient way to stem the tide.