Maternal Exercise Protects Offspring from Obesity and Insulin Resistance

母亲锻炼可保护后代免受肥胖和胰岛素抵抗

• 批准号: 8387023
• 负责人: Kevin Joseph Pearson
• 金额: $ 31.17万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8387023
• 关键词: Acetylation; Adult; Adult Children; Affect; Age; Behavior; Biological Assay; Blood Pressure; Body Composition; Cardiovascular Diseases; Commit; Consumption; CpG Islands; Development; Diabetes Mellitus; Diet; Discipline of Nursing; Disease; Embryo; Environment; Epidemic; Epigenetic Process; Exercise; Fasting; Female; Genes; Gestational Diabetes; Glucokinase; Glucose; Glucose Transporter; Health; Heart Diseases; Histone Acetylation; Home environment; Hour; Human; Hypertension; Incidence; Injection of therapeutic agent; Insulin; Insulin Receptor; Insulin Resistance; Insulin Signaling Pathway; Intervention; Laboratories; Lead; Liver; Longevity; Measures; Metabolic; Methylation; Modeling; Monitor; Mothers; Motor; Mus; Obese Mice; Obesity; Outcome; Parents; Partner in relationship; Pathology; Pathway interactions; Performance; Phenotype; Phosphorylation; Pilot Projects; Population; Pregnancy; Probability; Promoter Regions; Proteins; Publishing; Research; Role; Running; Skeletal Muscle; Termination of pregnancy; Testing; Tissues; Ursidae Family; Very Light Exercise; Western World; blood glucose regulation; design; epidemiology study; fasting glucose; feeding; glucose disposal; glucose tolerance; glucose-6-phosphatase; improved; insulin sensitivity; insulin signaling; insulin tolerance; leptin receptor; next generation; novel; offspring; pregnant; programs; protein expression; public health relevance; response; sedentary; stem; trend; unborn child

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.

描述（申请人提供）：宫内环境影响生长中胚胎的发育，不合适的环境可能导致终止妊娠。然而，新兴研究表明，更微妙的因素可能会影响后代的长期健康。例如，营养不良的怀孕母亲生下的后代较小，成年后肥胖、糖尿病和心脏病的发病率较高。到目前为止，大多数已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其后代的代谢紊乱。为了积极主动，选择母亲在怀孕期间自愿锻炼作为潜在的短期干预措施，以改善后代的健康结果。与未运动的母鼠相比，运动的母鼠所生的后代的空腹循环葡萄糖和胰岛素水平较低，并且葡萄糖处理和胰岛素敏感性显着改善。因此，我们对该提案的假设是，母亲在怀孕和哺乳期间的自愿锻炼将改善血糖调节并减少后代的肥胖和高血压。第一个目标是确定母亲自愿锻炼是否可以提高正常、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出现肥胖、胰岛素抵抗和高血压进展。第二个目标希望阐明运动母鼠所生后代持久胰岛素敏感性的机制，这可能是通过增强胰岛素信号传导来实现的。第三个目标将确定母亲运动是否可以作为干预措施来改善因母亲食用高热量饮食或妊娠糖尿病而导致的后代的病理结果。为了探索这些目标，雌性小鼠将被分为久坐组或自愿运动组。运动母鼠在交配前以及整个怀孕和哺乳期间可以 24 小时使用跑轮。成熟的后代将无法在研究的任何部分使用跑轮。将监测喂养标准或高热量饮食的后代的肥胖、葡萄糖和胰岛素耐受性以及高血压。这些研究将提供有关母亲锻炼对后代健康的潜在积极影响的重要信息。肥胖、糖尿病和心血管疾病已达到流行水平，针对妊娠的干预措施可能是遏制这种趋势的有效方法。