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了解和治疗肥胖症至关重要，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。以往的研究表明，在能量限制期间，只有基础代谢率和食物的热效应发生微小的变化，这意味着活动产热（AT）可能有助于在负能量平衡期间的能量调节。在这个建议中，我们将检查在瘦和肥胖的人类受试者的负能量平衡AT。在具体目标1中，我们将讨论瘦个体在能量限制期间AT降低的假设。在这里，我们不仅将确定非运动活动产热（NEAT）如何在1000千卡/天的负能量平衡中变化，而且还将梳理AT的组成部分如何变化。具体来说，我们将研究负能量平衡对坐、站、走、改变姿势和坐立不安产热的影响。在具体目标2中，我们将讨论肥胖与营养不良期间NEAT过度下降相关的假设。在这里，我们将限制肥胖和瘦的受试者的能量，并在喂养不足之前和之后测量NEAT及其组成部分。此外，为了确定肥胖和瘦受试者之间的差异是否仅与过度肥胖有关，或者与个体对肥胖的易感性有关，我们将类似地对一组肥胖后受试者进行喂养不足。我们的第三个具体目标是令人难以置信的兴奋。在这里，我们想确定除了能量限制之外，每天强制进行200千卡的步行是否会减弱瘦型、肥胖和肥胖后受试者的AT下降。我们想从机械论的角度了解这一点，以便深入了解意志AT如何受到强制行走的影响。此外，这将有助于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效益。总之，该计划将使我们能够第一次定义AT，NEAT及其组成部分在瘦个体负能量平衡期间如何变化。接下来，这些研究将为我们提供关于肥胖患者如何在负能量平衡期间适应能量的巨大见解。最后，我们将获得有关代谢的影响相结合的食物限制与步行计划兼容的法定机构所提倡的基本信息。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.