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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）：母亲肥胖会增加后代肥胖的风险，并且有大量证据表明胎儿和新生儿发育期间的编程会导致这种倾向。母乳喂养是公认的人类新生儿营养“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，母亲肥胖可能会抵消母乳喂养对哺乳后代代谢健康和肥胖风险的益处。我们的研究旨在了解母亲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倾向的产后贡献，区分产妇肥胖的具体影响和产妇食用高脂肪（HF）致肥胖饮食所造成的影响。我们的数据表明，来自肥胖母猪的牛奶选择性地编程了新生儿新陈代谢的肥胖变化。在最近的工作中，我们将这些变化与乙酰辅酶 A 羧化酶 1 (ACC1) 抑制导致的从头乳脂合成受损以及肥胖母猪生产的低脂乳联系起来。该提案的总体目标是使用肥胖小鼠模型结合创新的基因操作和定量代谢和成像方法来：（1）确定母亲肥胖对后代肥胖倾向的影响； (2) 详细说明肥胖母猪的牛奶对新生儿代谢的影响； (3) 定义 ACC1 和从头脂肪生成在导致新生儿肥胖的肥胖相关乳汁变化中的作用。正如本提案所述，对产后肥胖对新生儿代谢健康影响的生理和分子机制进行了详细的系统研究，为制定预防肥胖的新干预策略奠定了基础。