Brown adipose tissue and its metabolic correlates in human newborns and infants

人类新生儿和婴儿的棕色脂肪组织及其代谢相关性

基本信息

批准号：
8631085
负责人：
Claudia Buss
金额：
$ 19.3万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
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：
2013-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8631085
关键词：
Accounting Address Adolescence Adult Age-Months Anatomy Area Award Belief Biology Birth Blood Blood specimen Body Composition Brain Brown Fat Characteristics Childhood Data Development Discipline of obstetrics Dual-Energy X-Ray Absorptiometry Early identification Endocrine Energy Metabolism Exercise Expeditions Fatty acid glycerol esters Fishes Functional disorder Funding Glucose Goals Growth Heating Human Human Milk Immune Individual Infant Insulin Intervention Knowledge Label Life Literature Magnetic Resonance Imaging Maternal Behavior Measures Metabolic Mothers Nature Neonatal Newborn Infant Obesity Outcome Phase Play Pregnancy Process Protocols documentation Public Health Risk Role Sampling Scanning Sleep Staging Supraclavicular Testing Thermogenesis Time Tissues Translational Research United States National Institutes of Health Variant Vulnerable Populations Water base biophysical properties cohort cost energy balance feeding fetal glycemic control human data improved indexing infancy infant nutrition insulin sensitivity interest novel nutrition obesity risk population based postnatal prenatal prospective public health relevance

项目摘要

DESCRIPTION (provided by applicant): There is a major resurgence of interest in brown adipose tissue (BAT) biology following the relatively recent discoveries that, contrary to prior belief, BAT does in fact persist into adulthood and appears to play an important, beneficial role in reduced obesity/adiposity risk. The nature of BAT as a specialized heat-producing and energy- expending tissue, its presence in substantial amount in newborns, and its role in neonatal thermogenesis has long been established. However, very little is known about the relationship of BAT characteristics in early life in humans and its implications for obesity/adiposity and metabolic function in subsequent periods of life. Thus, as an important first step to addressing this broad issue, the specific aims of the current proposal are (1) to characterize in a sample of healthy human newborns inter-and intra-individual variation in the volume of BAT at birth and reduction in BAT mass over the first year of life, and (2) to study the associations of BAT mass at birth and BAT mass attrition over the first year of life with key biophysical, metabolic and other developmental parameters, including body composition, total energy expenditure and insulin sensitivity. A unique strength of our proposal is the availability f a cohort of newborns and infants who are extensively characterized over the course of their intrauterine and postnatal life. We are currently conducting NIH-funded prospective, longitudinal projects in a representative, population-based cohort from birth (T1) and over the early postnatal growth phase until 12 months age (T2). These births occur in mothers who, in turn, were extensively and longitudinally studied over the entire course of their index pregnancy. The infant assessments include serial measures of growth, body composition, energy expenditure, and insulin sensitivity, and magnetic resonance imaging (MRI) assessments of the brain during natural sleep. The current R21 proposal seeks funds to incorporate the study of an additional, related outcome of high interest and relevance - newborn and infant brown adipose tissue (BAT) volume - using a non-invasive water-fat separated MRI protocol that our group has validated for the use in human infants. Within the 2-year time frame of the current proposal we propose to assess BAT volume in a subpopulation of N=100 infants longitudinally from birth until 12 months age. Our proposal addresses the following knowledge gaps: a) the developmental ontogeny of brown adipose tissue depots from birth until 12 months age; and b) the consequences and implications of BAT depots in infancy for subsequent obesity risk and associated metabolic dysfunction. The significance and impact of this study derives from the importance of achieving a better understanding of the underlying processes that increase risk or vulnerability for obesity (adiposity) and metabolic dysfunction. This study will collect novel data (serial measures of infant brown adipose tissue mass) and produce results that set the stage for the development of subsequent, testable hypotheses and translational research with important implications for early identification of risk/vulnerable populations, in order to inform the subsequent development of primary and secondary intervention strategies.

描述（由申请人提供）：在相对较新的发现之后，棕色脂肪组织（BAT）生物学的兴趣很大，与先前的信念相反，BAT实际上确实持续成年，并且似乎在降低肥胖/肥胖风险中起着重要的，有益的作用。长期以来已经建立了蝙蝠作为一种专门的热产热和消耗组织，其在新生儿中大量的存在以及其在新生儿生热发生中的作用。然而，对于人类早年的蝙蝠特征的关系及其对肥胖/肥胖和代谢功能的影响很少。因此，作为重要的第一 step to addressing this broad issue, the specific aims of the current proposal are (1) to characterize in a sample of healthy human newborns inter-and intra-individual variation in the volume of BAT at birth and reduction in BAT mass over the first year of life, and (2) to study the associations of BAT mass at birth and BAT mass attrition over the first year of life with key biophysical, metabolic and other developmental parameters, including body composition, total energy expenditure and胰岛素灵敏度。我们提议的一个独特优势是，在宫内和产后生活的过程中，众多新生儿和婴儿的可用性。目前，我们正在从出生（T1）和产后早期到12个月的早期（T2）的代表性，基于人群的队列中进行NIH资助的前瞻性，纵向项目（T2）。这些出生发生在母亲中，这些母亲反过来在整个指数怀孕过程中都经过广泛而纵向研究。婴儿评估包括生长，身体成分，能量消耗和胰岛素敏感性以及自然睡眠期间大脑的磁共振成像（MRI）评估的序列测量。当前的R21提案寻求资金纳入对高兴趣和相关性的其他相关结果 - 新生儿和婴儿棕色脂肪组织（BAT）体积 - 使用非侵入性水脂分离的MRI协议，该协议已验证了该协议以在人类婴儿中使用。在当前提案的两年时间范围内，我们提议从出生到12个月大的纵向评估n = 100个婴儿的亚群中的蝙蝠量。我们的提议解决了以下知识差距：a）从出生到12个月大的棕色脂肪组织仓库的发育发育； b）蝙蝠仓库对随后的肥胖风险和相关代谢功能障碍的后果和影响。这项研究的重要性和影响来自于更好地理解增加肥胖（肥胖）和代谢功能障碍的风险或脆弱性的基本过程的重要性。这项研究将收集新的数据（婴儿棕色脂肪组织质量的序列测量），并产生结果，为随后的可检验的假设和转化研究树立了阶段，对早期识别风险/易受伤害人群的重要意义，以便为随后的一级和二级干预策略提供信息。