POST-PRANDIAL NUTRIENT PARTITIONING IN HUMANS

提案（改编自申请人的摘要）： 候选人是追求在学术医学领域的职业生涯， 内分泌学和代谢，其具体的研究目标是成为 在燃料代谢和肥胖领域的独立研究员。 的 候选人的直接目标是发展坚实的基础和技能 过渡到独立的研究生涯所必需的。 导师 以病人为导向的研究职业发展奖将有助于使 候选人通过完成拟议的研究来实现这些短期目标 并遵循所概述的具体职业发展计划。 此外该 机构和导师提供了一个出色和支持性的环境。 拟议研究项目的目标是更好地了解 短期过度喂养对营养物质代谢的影响。 肥胖是一 严重和日益增长的公共卫生问题在美国的病理生理 肥胖症发病率上升的原因并不在于 明确定义，但可能涉及环境之间的错误相互作用 因素，有利于积极的能量平衡，与生物重量 基因“高危”个体的监管系统。 的个人 在目前的环境中，遗传倾向于瘦的人可能能够 更快、更准确地感知和应对过量的能量摄入， 那些容易肥胖的人。 据推测， 出现短暂的胰岛素抵抗反应过度喂养， 优先将膳食脂肪递送到氧化活性组织，导致 增加脂肪氧化。 这也可能与增加的感觉有关 这些个体的饱腹感。 最终的结果是， 机制将保护瘦的个体免受过度的体重增加。 测试 这些想法，研究精益和减少肥胖的主题，经过三天的 期间的过度喂养50%以上的基础热量需求，提出。 具体来说，研究胰岛素敏感性的脂肪分解，葡萄糖 处置和葡萄糖生产使用胰岛素钳和示踪技术， 以及检测标记葡萄糖代谢命运的示踪膳食研究 和脂肪酸。 这些研究将包括间接 量热法、示踪剂氧化、肢体平衡和组织取样， 膳食相关营养代谢的综合观点。 互补 关于过度喂食对饱腹感和适口性影响的研究也在 提出了 这些研究将提供对生物学的深入了解， 容易体重增加和恢复，并将为未来奠定基础 研究存在于肥胖和肥胖症患者中的营养代谢异常， 肥胖前个体。

PROPOSAL (Adapted from the applicant's abstract): The long-term goal of the candidate is to pursue a career in academic medicine in the field of endocrinology and metabolism with a specific research goal of becoming an independent researcher in the area of fuel metabolism and obesity. The candidate's immediate goals are to develop the strong foundation and skills necessary for the transition to an independent research career. The Mentored Patient-Oriented Research Career Development Award will help to enable the candidate to reach these short-term goals by completing the proposed studies and following the specific career development plan outlined. In addition, the institution and mentors provide an outstanding and supportive environment. The goal of the proposed research project is to gain a better understanding of the effects of short-term overfeeding on nutrient metabolism. Obesity is a serious and growing public health problem in the U.S. The pathophysiological processes that underlie this increasing prevalence of obesity have not been clearly defined but likely involve faulty interactions between environmental factors, which favor positive energy balance, with biological weight regulatory systems in genetically "at risk" individuals. Individuals who are genetically predisposed to leanness in the current environment may be able to sense and respond to excess energy intake more rapidly and accurately than those predisposed to obesity. It is hypothesized that lean individuals develop transient insulin resistance in response to overfeeding and may preferentially deliver dietary fat to oxidatively active tissues, leading to increased fat oxidation. This may also be associated with an increased sense of satiety in these individuals as well. The end result is that these mechanisms will protect lean individuals from excessive weight gain. To test these ideas, studies of lean and reduced-obese subjects, following a three-day period of overfeeding 50% above basal caloric requirements, are proposed. Specifically, studies on the insulin sensitivity of lipolysis, glucose disposal, and glucose production using insulin clamp and tracer techniques, as well as tracer meal studies examining the metabolic fate of labeled glucose and fatty acids, are proposed. These studies will include indirect calorimetry, tracer oxidation, limb balance, and tissue sampling to give a comprehensive view of meal associated nutrient metabolism. Complementary studies on the effects of overfeeding on satiety and palatability are also proposed. These studies will provide insight into the biology that predisposes to weight gain and regain and will lay the groundwork for future studies of the abnormalities in nutrient metabolism that exist in obese and preobese individuals.