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）：孕产妇肥胖增加了后代肥胖的风险，并且有大量证据表明，在胎儿和新生儿发育期间的编程都有助于这种倾向。母乳喂养是人类新生儿营养的公认的“黄金标准”，与儿童肥胖风险降低有关。但是，来自人类和动物研究的新兴证据表明，母亲肥胖可能会超越母乳喂养对养育后代的代谢健康和肥胖风险的好处。我们的研究旨在理解母体肥胖影响其下剂量对肥胖的代谢易感性的机制。我们建立了一个小鼠模型，使我们能够定义孕产妇肥胖对新生儿代谢健康和肥胖倾向的贡献，从而区分了孕产妇肥胖的特定作用与孕产妇食用高脂（HF）肥胖饮食所赋予的特定作用。我们的数据记录肥胖水坝的牛奶有选择地对新生儿代谢的青少年变化进行编程。在最近的工作中，由于抑制乙酰辅酶A羧化酶-1（ACC1）以及肥胖水坝的产生脂质牛奶，这些变化与从头牛奶脂质合成受损相关。该提案的总体目标是结合创新的遗传操纵以及定量代谢和成像方法的结合：（1）定义孕产妇肥胖对异性肥胖症的影响；（2）详细介绍牛奶Frm肥胖水坝对新生儿代谢的影响；（3）在促进新生儿肥胖症的牛奶中与肥胖相关的改变中定义了ACC1和从头脂肪生成的作用。如本提案中概述的那样，孕产妇肥胖对新生儿代谢健康的产后作用的生理和分子机制的详细系统研究构成了开发新干预策略以防止肥胖的基础。