Phenotypic and metabolic characteristics in early childhood leading to obesity

 描述（由申请人提供）：根据疾病控制和预防中心的数据，2 至 5 岁儿童中有 23.8% 超重，11.1% 肥胖。研究表明，两岁时就开始肥胖的儿童成年后更有可能肥胖。因此，在美国，四分之一的儿童在以后的生活中面临肥胖的风险。在许多研究中，婴儿期的体重变化速度与以后的肥胖风险相关。然而，大多数研究报告的是人体测量而不是身体脂肪量测量。目前尚不清楚出生后头两年脂肪量和无脂量增加的哪种模式会导致肥胖。同样，研究也很少 研究了婴儿和儿童的脂肪量分布，特别是在快速时期 增长和能源需求增加。我们的初步分析表明，虽然母亲 BMI 和能量摄入有助于体重速度与 2 岁时超重/肥胖状态之间的关联，但可能还有其他因素导致婴儿体重速度加快。我们假设体重速度也是由新陈代谢的变化驱动的，因此与童年时期保持正常体重的婴儿相比，超重或肥胖的婴儿会形成能量节约表型，导致体重增加更大。因此，它们能够更有效地储存多余的热量，从而导致脂肪量的积累增加。尽管这一点尚未在人类中进行过研究，也没有数据表明这可能如何影响各种脂肪库，但这种能量节约表型得到了动物模型的支持，表明母体肥胖会影响子代在子宫内的新陈代谢，导致能量消耗和脂肪酸氧化率降低。该应用的目的是通过测量婴儿和儿童在生命的头两年内的能量摄入、总能量消耗率、脂肪酸氧化率以及脂肪量增加和分布，同时控制重要的混杂因素，来弥补这些知识差距。我们将检验这样一个假设：婴儿期体重过度增加是由较高的能量摄入和较低的能量消耗以及脂肪酸氧化率驱动的，从而导致更大的脂肪量增加。第一个目标是确定 6、12 和 24 个月大的婴儿和儿童的体重速度、能量摄入和能量消耗之间的关联。为此，将使用双标签水来评估总能量消耗。第二个目标是使用 6、12 和 24 个月大的婴儿和儿童的稳定同位素技术确定体重速度与脂肪酸氧化之间的关联。第三个目标将使用双能 X 射线评估婴儿和儿童在生命的头两年内的脂肪量增加和分布 吸收测定法和定量核磁共振技术。

 DESCRIPTION (provided by applicant): According to the Centers for Disease Control and Prevention, 23.8 percent of children age 2 to 5 years are overweight and 11.1 percent are obese. Studies have demonstrated that children who become obese as early as age 2 years are more likely to be obese as adults. Accordingly, 1 in 4 children is at risk for developing obesity later in life in the United States. Weight velocity during infancy has been associated with later risk of obesity in numerous studies. However, most studies have reported on anthropometric rather than body fat mass measures. It is unknown which patterns of fat mass and fat free mass accretion during the first two years of life yield obesity development. Similarly, very few studies have investigated fat mass distribution in infants and children especially during a period of rapid growth and increased energy needs. Our preliminary analyses suggest that while maternal BMI and energy intake contribute to the association between weight velocity and overweight/obese status at age 2 years, there are likely other factors that lead to greater weight velocity in infany. We postulate that weight velocity is also driven by a shift in metabolism such that infants who will become overweight or obese develop an energy sparing phenotype leading to greater weight gain compared to infants who remain normal weight during childhood. Therefore they are more efficient at storing excess calories leading to increased accumulation of fat mass. Though this has not been studied in humans and no data exist to suggest how this might influence various fat depots, this energy sparing phenotype is supported by animal models demonstrating that maternal obesity programs offspring metabolism in utero resulting in decreased energy expenditure and fatty acid oxidation rates. The objective of this application is to address these gaps in knowledge by measuring energy intake, total energy expenditure rates, fatty acid oxidation rates, and fat mass accretion and distribution of infants and children during the first two years of life while controlling for important confounding factors. We will test the hypothesis that excessive weight gain during infancy is driven by both greater energy intake and lower energy expenditure and fatty acid oxidation rates, resulting in greater fat mass accretion. The first aim will determine the associations between weight velocity, energy intake and energy expenditure of infants and children at age 6, 12 and 24 months. For this aim, total energy expenditure will be evaluated using doubly-labelled water. The second aim will determine the associations between weight velocity and fatty acid oxidation of infants and children using stable isotope techniques at age 6, 12 and 24 months. The third aim will evaluate fat mass accretion and distribution in infants and children during the first two years of life using dual energy X-ray absorptiometry and quantitative nuclear magnetic resonance techniques.