Protein Quality Early in Life: Mechanisms of Growth and Later Obesity Development

摘要 在生命的头两年，体重的快速增加容易导致晚年肥胖。然而，有一个 在应该向婴幼儿提供什么饮食建议的知识方面存在根本差距 促进最佳生长，防止体重快速增加。膳食蛋白质摄入量被认为是一个危险因素。 因为它会加速婴幼儿的体重和脂肪增加，这主要是基于对乳制品蛋白质的研究。 然而，潜在的机制尚不清楚。这些发现一直是最近 建议将出生时的蛋白质摄入量减少到24个月。尚不清楚的是，是否所有的蛋白质 货源也有同样的提重效果。我们课题组进行了随机对照研究 在6至12个月大的婴儿中食用以肉类或乳制品为基础的补充饮食的试验。生长 数据显示，以乳制品为基础的补充饮食，而不是肉类，会导致线性增长受损，并增加 超重的风险。这一拟议项目的目标是调查潜在的机制和 通过粪便确定哪些介质可以预测该队列中的不同生长模式 微生物组/元基因组学、血清代谢组学和双标记水技术。尽管 应聘者拥有儿科营养和进行随机对照试验的专业知识，培训 对肥胖发展和研究方法的机械性调查对于实现 长期目标是成为儿科营养领域的领导者，重点实施有效的干预措施 在生命早期促进最佳生长和预防肥胖。 这份职业发展申请书向应聘者提出了为期4年的多学科培训计划， 他是一名四年级博士后，正在过渡到初级教职。精心制定的培训计划 由应聘者和指导团队完成，包括1)实践经验 微生物组/元基因组学、代谢组学分析和数据解释；2)实践经验 对婴儿的身体成分和总能量消耗进行双标记水方案 和蹒跚学步的孩子，加上样本分析和数据解释；3)定期与导师会面以监督 项目进展、短期和长期目标取得的成就，以及教学培训；4)高级 微生物组、代谢组学和生物统计学方面的课程；5)领导力培训和计划 管理层。科罗拉多大学安舒茨医学院是世界领先的研究机构和 为应聘者提供良好的研究和培训环境，以促进成功的 过渡到儿科营养和早期肥胖预防方面的独立职业。

ABSTRACT Rapid weight gain during the first two years of life predisposes to later-in-life obesity. However, there is a fundamental gap in knowledge of what dietary recommendations should be provided to infants and toddlers to promote optimal growth and prevent rapid weight gain. Dietary protein intake is considered a risk factor because it accelerates weight and fat gain in infants and toddlers, based primarily on research of dairy protein. However, the underlying mechanisms are not clear. These findings have been the basis of recent recommendations to reduce protein intake from birth to 24 months. What is not known is whether all protein sources have the same weight-accelerating effect. Our research group conducted a randomized controlled trial in infants consuming a meat- or dairy-based complementary diet from 6 to 12 months of age. Growth data showed that a dairy-based complementary diet, not meat, leads to impaired linear growth and increased risk for being overweight. The objective of this proposed project is to investigate the underlying mechanisms and determine which mediators are predictive for the different growth patterns in this cohort via fecal microbiome/metagenomics, serum metabolomics and doubly labeled water technique. Although the candidate has expertise in pediatric nutrition and conducting randomized controlled trials, training in mechanistic investigations of obesity development and research methodologies are critical to achieve the long-term goal of becoming a leader in pediatric nutrition focusing on implementing effective interventions early in life for optimal growth and obesity prevention. This career development application proposes a 4-year multidisciplinary training program to the candidate, who is a 4th year postdoctoral fellow transitioning to a junior faculty position. A well-developed training plan by the candidate and the mentoring team is in place, including 1) Hands-on experience of microbiome/metagenomics, metabolomics analysis and data interpretation; 2) Hands-on experience of conducting the doubly labeled water protocol for body composition and total energy expenditure in infants and toddlers, plus sample analysis and data interpretation; 3) Regular meetings with mentors to monitor project progress, achievements towards the short- and long-term goals, and didactic trainings; 4) Advanced coursework in microbiome, metabolomics and biostatistics; 5) Training in leadership and program management. University of Colorado Anschutz Medical Campus is world-leading research institution and provides the candidate an excellent research and training environment which facilitates a successful transition to an independent career in pediatric nutrition and early-in-life obesity prevention.