The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk

生长研究、血糖范围以及后代体重和肥胖对母乳的反应

基本信息

批准号：
10595445
负责人：
Brigid Ellen Gregg
金额：
$ 200.79万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10595445
关键词：
2 year old Accounting Address Adipocytes Anabolism Ancillary Study Beta Cell Body Composition Body fat Body mass index Breast Epithelial Cells Breast Feeding Categories Cells Child Childhood Development Diet Dissection Enrollment Environment Epithelial Cells Exposure to Fatty Acids Follow-Up Studies Food Functional disorder Funding Gene Expression Gene Expression Profile Gestational Diabetes Glucose Glucose Metabolism Disorders Goals Growth Health Human Human Milk Hyperglycemia Hypertrophy Infant Insulin Resistance Intervention Knowledge Lactation Length Linoleic Acids Linolenic Acids Lipids Mammary gland Measures Metabolic Metabolic Diseases Metabolism Milk Modeling Mothers National Institute of Child Health and Human Development Nutrient Obesity Outcome Palmitic Acids Pathologic Pathway interactions Phenotype Postpartum Period Predisposition Pregnancy Public Health Regulation Reproducibility Research Risk Risk Reduction Sampling Scientist Shapes Testing Time Translational Research United States National Institutes of Health Validation Variant Weight Woman adipocyte differentiation adverse pregnancy outcome cardiometabolic risk cohort early childhood experience high body mass index improved in utero in vitro testing infant adiposity inter-individual variation lactation period lactogenesis lipid biosynthesis mammary gland development maternal condition maternal diabetes maternal hyperglycemia maternal obesity metabolic phenotype mother nutrition novel nutrition obesity in children offspring post pregnancy prenatal exposure prospective response screening transcriptomics translational study

项目摘要

ABSTRACT Maternal metabolism during pregnancy is a key contributor to developmental origins of metabolic disease. Offspring exposed to maternal hyperglycemia and obesity have increased rates of obesity and disordered glucose metabolism. The lactation period is also a critical window for programming. Lactogenesis initiates in the second half of gestation, thus human milk (HM) biosynthesis is susceptible maternal metabolism. Interindividual variation in HM nutrients reveals the influence of maternal metabolism on milk biosynthesis. A knowledge gap exists as to whether HM composition alters developmental pathways of offspring programmed in utero. Maternal metabolic states including gestational diabietes (GDM) and obesity alter HM nutrient profiles, including milk fatty acids (FA). Our studies identified altered HM linoleic acid and dihomo-gamma-linolenic acid (DGLA) in conditions of maternal diabetes, hyperglycemia, and obesity, as well as HM palmitic acid and DGLA associations with infant growth. However, any impact of maternal metabolism across the entire range of glycemia on both HM composition and offspring programming has not been evaluated in context of detailed profiling of in utero exposures. Our goal is to understand how HM susceptibility to maternal metabolism impacts offspring metabolism, identifying interventions to mitigate adverse developmental programming. This proposal’s objective is to determine the impact of maternal glycemia in pregnancy on HM composition and effects of HM nutrients on offspring adiposity. Translational science approaches will determine how maternal glycemia alters mammary gland epithelial cell gene expression and how HM lipids across the range of maternal glycemia regulate infant adipoctyes. Our overarching hypothesis is that maternal glycemia in normal and pathologic ranges impacts HM composition, which in turn influences offspring metabolic programming as reflected by early childhood adiposity. Capitalizing on the detailed metabolic phenotyping of the GO MOMs cohort, we will conduct prospective HM profiling at 1, 2 and 6 months post-partum in a cohort of 450 women to associate maternal glycemia during and after pregnancy, focusing on HM lipids known to regulate offspring adiposity (Aim 1). Mammary epithelial cells shed in expressed HM will be evaluated using transcriptomics (SubAim 1). For reproducibility, HM lipids will be compared to a separate validation cohort enrolling women with GDM. We will measure offspring body composition to discern adiposity at months 1, 2, and 6 and 2 years, accounting for childhood diet (Aim 2). A human infant preadipocyte strain will be exposed to HM lipids collected and grouped by quartiles of maternal glycemia to determine mechanisms altering infant adipocyte development (Aim 3). Completing the aims will define HM composition in a pregnancy cohort with comprehensive metabolic profiling throughout pregnancy and lactation across the range of glycemia and BMI. Offspring growth and translational studies will advance understanding of how lactation exposures modify in utero programming. This will further the field by revealing interventions to reduce risk of adverse offspring metabolic health.

抽象的怀孕期间的孕产妇代谢是代谢疾病发育起源的关键因素。暴露于产妇高血糖和肥胖的后代有肥胖症的率增加葡萄糖代谢。哺乳期也是编程的关键窗口。裂伤开始妊娠的后半部分，因此人乳（HM）生物合成是易感材料代谢。 HM养分中个体差异揭示了物物代谢对牛奶生物合成的影响。一个关于HM组成是否改变了后代编程的发展途径的知识差距在子宫里。孕产妇的代谢状态在内包括牛奶脂肪酸（FA）。我们的研究确定了改变的HM亚油酸和二氢γ-氨基酸的改变（DGLA）在母体糖尿病，高血糖和肥胖症以及HM棕榈酸和DGLA的条件下与婴儿生长的关联。但是，在整个范围内的物物代谢的任何影响 HM组成和后代编程的血糖均未详细评估在子宫内暴露中分析。我们的目标是了解HM对母性代谢的敏感性影响后代的代谢，确定干预措施以减轻不良发展节目。这提案的目标是确定孕产妇血糖对怀孕对HM组成和 HM养分对后代肥胖的影响。翻译科学方法将决定母亲血糖改变乳腺上皮细胞基因表达以及HM脂质如何跨越范围母体血糖调节婴儿脂肪症。我们的总体假设是正常的Matar血糖病理性的范围会影响HM组成，这反过来影响后代代谢编程幼儿肥胖反映。利用GO妈妈的详细代谢表型队列，我们将在450名妇女的队列中1、2和6个月进行预期的HM分析在怀孕期间和之后缔合母亲血糖，重点是已知的HM脂质，以调节后代肥胖（目标1）。将使用转录组学评估以表达HM的乳腺上皮细胞（Subaim 1）。为了重现性，将将HM脂质与单独的验证队列进行比较与GDM。我们将测量后代身体组成，以辨别第1、2和6和2年的肥胖性，会计儿童饮食（AIM 2）。人类婴儿前脂肪细胞菌株将暴露于收集的HM脂质并由母体血糖的四分位数分组，以确定改变婴儿脂肪细胞发育的机制（目标3）。完成目标将定义与全面代谢的怀孕队列中的HM成分在整个怀孕和哺乳期遍布糖果和BMI范围内。后代增长和翻译研究将进一步了解子宫编程中泌乳暴露如何修饰。这将通过揭示干预措施来进一步进一步，以减少不良后代代谢健康的风险。