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Postnatal Actions of Maternal Obesity on Neonatal Metabolic Health

母亲肥胖对新生儿代谢健康的产后作用

基本信息

批准号：
8703153
负责人：
Paul S. Maclean
金额：
$ 31.26万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8703153
关键词：
Acetyl-CoA Carboxylase Adult Affect Animals Breast Epithelial Cells Breast Feeding Carbohydrates Cells Chronic Consumption Data Development Diet Discipline of Nursing Disease Energy Intake Energy Metabolism Environment Epidemic Exhibits Fatty acid glycerol esters Food Fostering Foundations Future Goals Gold Growth Health Healthcare Human Human Milk Image Impairment Incidence Insulin Resistance Intervention Investigation Knock-out Lactation Lead Life Link Lipids Macronutrients Nutrition Mammary gland Metabolic Metabolic Diseases Metabolic syndrome Metabolism Milk Molecular Neonatal Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Outcome Phenotype Physiological Predisposition Production Property Proteins Publishing Risk Role Solid Source Staging Testing Time Tracer Transgenic Mice United States Weaning Work care burden energy balance feeding fetal genetic manipulation in utero innovation insight lipid biosynthesis meetings mortality mouse model neonatal human neonate nutrition obesity in children obesity risk obesogenic offspring postnatal prevent programs public health relevance pup research study

项目摘要

DESCRIPTION (provided by applicant): Maternal obesity increases the risk for offspring to become obese, and there is substantial evidence to suggest that programming during both fetal and neonatal development contributes to this predisposition. Breastfeeding, the recognized "gold standard" for human neonatal nutrition, is associated with reduced childhood obesity risk. However, emerging evidence from human and animal studies suggests that maternal obesity may override the benefits of breastfeeding on the metabolic health and obesity risk of nursing offspring. Our study is directed at understanding the mechanisms by which maternal obesity influences the metabolic predisposition of their off-spring to obesity. We established a mouse model that allows us to define postnatal contributions of maternal obesity to neonatal metabolic health and obesity predisposition, distinguishing the specific effects of maternal obesity from those imparted by maternal consumption of a high fat (HF) obesigenic diet. Our data document that milk from obese dams selectively programs obesigenic changes in neonatal metabolism. In recent work we linked these changes to impaired de novo milk lipid synthesis due to inhibition of acetyl- CoA carboxylase-1 (ACC1), and the production of lipid-poor milk by obese dams. The overall goals of this proposal are to use obese mouse models in conjunction with innovative genetic manipulation and quantitative metabolic and imaging approaches to: (1) define the effects of maternal obesity on off-spring obesity predisposition; (2) detail the effects of milk frm obese dams on neonatal metabolism; (3) define the roles ACC1 and de novo lipogenesis in the obesity-associated alterations in milk that promote neonatal obesity. The detailed systematic investigation of the physiological and molecular mechanisms underlying postnatal effects of maternal obesity on neonatal metabolic health, as outlined in this proposal, form the foundation for development of new intervention strategies to prevent obesity.

描述（由申请人提供）：母体肥胖增加了后代肥胖的风险，并且有大量证据表明，胎儿和新生儿发育期间的编程有助于这种易感性。母乳喂养是公认的人类新生儿营养的“黄金标准”，与降低儿童肥胖风险有关。然而，来自人类和动物研究的新证据表明，母亲肥胖可能会压倒母乳喂养对代谢健康和喂养后代肥胖风险的好处。我们的研究旨在了解母体肥胖影响其后代肥胖代谢倾向的机制。我们建立了一个小鼠模型，使我们能够定义产妇肥胖对新生儿代谢健康和肥胖易感性的产后贡献，区分产妇肥胖的具体影响与产妇食用高脂肪（HF）肥胖饮食所带来的影响。我们的数据表明，来自肥胖母鼠的乳汁选择性地导致新生儿代谢的肥胖性变化。在最近的工作中，我们将这些变化与由于乙酰辅酶A羧化酶-1（ACC 1）的抑制而导致的新生乳脂质合成受损以及肥胖母鼠产生的低脂乳联系起来。本研究的总体目标是利用肥胖小鼠模型，结合创新的遗传操作和定量代谢及成像方法：（1）确定母体肥胖对后代肥胖倾向的影响;（2）详细说明来自肥胖母体的牛奶对新生儿代谢的影响;（3）确定ACC 1和新生脂肪生成在促进新生儿肥胖的与肥胖相关的乳汁改变中的作用。详细的系统调查的生理和分子机制的产妇肥胖对新生儿代谢健康的影响，在这个建议中概述，形成新的干预策略，以防止肥胖的发展的基础。