POST-PRANDIAL NUTRIENT PARTITIONING IN HUMANS

建议书(改编自申请者的摘要)： 应聘者的职业生涯是在学术医学领域 内分泌学和新陈代谢研究的具体目标是成为 燃料代谢和肥胖领域的独立研究员。这个 应聘者的近期目标是发展坚实的基础和技能 这是向独立研究生涯过渡所必需的。被指导者 以病人为本的研究生涯发展奖将有助于 通过完成建议的研究来实现这些短期目标的候选人 并遵循所概述的具体职业发展计划。此外， 机构和导师提供了一个优秀和支持性的环境。 拟议的研究项目的目标是更好地了解 短期超量喂养对营养物质代谢的影响。肥胖是一种 美国日益严重的公共卫生问题--病理生理学 肥胖症日益流行的基础过程并不是 定义明确，但可能涉及环境之间有缺陷的相互作用 有利于正能量平衡的因素，与生物量 基因“高危”个体的监管系统。个人谁是 在当前的环境中，遗传倾向于瘦身的人或许能够 更快速、更准确地感知和响应过量的能量摄入 那些容易肥胖的人。据推测，瘦的人 出现短暂的胰岛素抵抗，以应对过度喂养，并可能 优先将膳食脂肪输送到氧化活性组织，导致 脂肪氧化增加。这也可能与感官的增强有关 这些人的满足感也很强。最终的结果是，这些 这些机制将保护苗条的个人免受体重过度增加的影响。为了测试 这些想法是对瘦身和减重受试者的研究，经过三天的研究 建议在超过基础热量需要量50%的时间内过量喂养。 具体地说，脂肪分解、葡萄糖对胰岛素敏感性的研究 利用胰岛素钳和示踪技术处理和生产葡萄糖，如 以及检测标记葡萄糖的代谢命运的示踪膳食研究 和脂肪酸，被提出。这些研究将包括间接的 量热法、示踪剂氧化、肢体平衡和组织取样 全面了解与膳食相关的营养代谢。互补性 关于过量喂养对饱腹感和适口性的影响的研究也在进行。 建议。这些研究将提供对生物学的洞察 容易增加体重和恢复体重，将为未来奠定基础 肥胖症患者营养代谢异常的研究进展 肥胖前期的个体。

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.