Nutritional Restriction and Activity Thermogenesis

描述(由申请人提供)：人类如何适应负能量平衡对于理解能量储存的生理学以及更广泛地说哺乳动物如何在食物短缺期间维持能量储存至关重要。此外，了解负能量平衡对于理解和治疗肥胖至关重要，肥胖症在发达国家很流行。在负能量平衡期间，脂肪储存减少，能量消耗下降。以前的研究证明，在能量限制期间，基础代谢率和食物的热效应只发生很小的变化，这意味着在负能量平衡期间，活动生热作用(AT)可能对能量调节有实质性的贡献。在这项建议中，我们将检查瘦削和肥胖受试者在负能量平衡期间的AT。在特定的目标1中，我们将解决这样的假设，即瘦肉型个体在能量限制期间AT降低。在这里，我们不仅要弄清非运动性生热(NEAT)在1000千卡/天的负能量平衡中是如何变化的，而且还将梳理AT的成分是如何变化的。具体地说，我们将研究负能量平衡对坐姿、站立、行走、变换姿势和坐立不安生热的影响。在特定的目标2中，我们将解决这样的假设，即肥胖与喂养不足期间整洁程度的夸大下降有关。在这里，我们将限制肥胖和瘦的受试者的能量，并测量喂养不足前后的Nat及其成分。此外，为了确定肥胖者和消瘦者之间的差异是否仅与过度肥胖有关，还是与个体对肥胖症的易感性有关，我们将同样对一组后肥胖者进行喂养不足。我们的第三个具体目标令人难以置信地兴奋。在这里，我们想要确定在限制能量的基础上，每天强制步行200千卡，是否可以缓解瘦身、肥胖和肥胖后受试者进食不足时AT的下降。我们想在一定程度上从机械论的角度了解这一点，以便深入了解强制行走对意志性AT的影响。此外，这将帮助我们更好地了解如何治疗肥胖患者，并确定步行计划与能量限制相结合的能量益处。总而言之，这个项目将使我们第一次确定在瘦身个体的负能量平衡过程中，AT、NEAT及其成分是如何变化的。接下来，这些研究将为我们提供关于肥胖患者在负能量平衡期间如何精力充沛地适应的巨大洞察力。最后，我们将获得有关将食物限制与步行计划相结合的代谢影响的基本信息，该计划与法定机构倡导的步行计划相兼容。这些研究将有助于更好地理解负能量平衡期间发生的能量适应，以及如何最好地治疗肥胖症患者。

DESCRIPTION (provided by applicant): How humans adapt to negative energy balance is critical for understanding the physiology of energy storage and more broadly how mammals maintain energy stores during food scarcity. Also, understanding negative energy balance is crucial for understanding and treating obesity, which is epidemic in developed countries. During negative energy balance, fat stores diminish and energy expenditure declines. Previous studies have documented that during energy restriction, only small changes in basal metabolic rate and the thermic effect of food occur, implying that activity thermogenesis (AT) may contribute substantively to energy modulation during negative energy balance. In this proposal we will examine AT during negative energy balance in lean and obese human subjects. In Specific Aim 1 we will address the hypothesis that AT decreases during energy restriction in lean individuals. Here, we will not only ascertain how non-exercise activity thermogenesis (NEAT) changes during 1000 kcal/day negative energy balance but also tease apart how the components of AT change. Specifically, we will study the effects of negative energy balance on, sitting, standing, walking, changing posture and fidgeting thermogenesis. In Specific Aim 2 we will address the hypothesis that obesity is associated with exaggerated decline in NEAT during underfeeding. Here, we will energy restrict obese and lean subjects and measure NEAT and its components before and after underfeeding. Also, to ascertain whether differences between the obese and lean subjects relate to excess adiposity alone or to the susceptibility of an individual to obesity, we will similarly underfeed a group of post-obese subjects. Our third specific aim is incredibly exciting. Here, we want to determine whether an imposed 200 kcal/day of walking in addition to energy restriction, attenuates the decline in AT with underfeeding in lean, obese and post-obese subjects. We want to know this, in part, from a mechanistic perspective in order to gain insight into how volitional AT is impacted by imposed walking. Also, this will help us to better understand how to treat our obese patients and to define the energetic benefit of combining a walking program with energy restriction. In conclusion, this program will allow us to define for the first time how AT, NEAT and its components change during negative energy balance in lean individuals. Next, these studies will provide us with enormous insight regarding how obese patients adapt energetically during negative energy balance. Finally, we will gain fundamental information regarding the metabolic implications of combining food restriction with a walking program compatible to that advocated by statutory agencies. These studies will lead to improved understanding of the energetic adaptation that occurs during negative energy balance and how best to treat patients with obesity.