Regulators of Food Intake

能量摄入和膳食中的常量营养素组成是能量平衡方程式中最难衡量的部分。在一项对预测食物摄入量的因素的自然历史研究中，使用住院的电脑自动售货机系统，测量了180多个人的食物摄入量。在不止一次接受研究的个体中，组内相关系数非常高(r=0.9)，这表明尽管这些研究是在住院环境中进行的，但重复性很强。 这项研究表明，较高的呼吸商，即碳水化合物氧化与脂肪氧化的比率，预测体重增加，也预测体重增加。呼吸商最能预测食物摄入量的成分是较高的碳水化合物氧化，表明碳水化合物(可能是糖原)平衡在调节短期食物摄入量中的作用。然而，在一项后续研究中，我们没有发现糖原耗竭会增加食物摄入量。如上所述，呼吸商是碳水化合物与脂肪氧化的比率。中枢下丘脑长链脂肪酸信号可以影响食物摄入量和外周脂肪氧化。因此，我们正在计划未来的研究，调查这些脂肪酸在控制食物摄入量中的作用。特别是，我们正在开展一项研究，调查鼻腔给药一种长链脂肪酸，并随后测量食物摄入量。 我们还证明，食物摄入量最重要的决定因素之一是脱脂质量。脱脂体重(根据身高调整)和食物摄入量之间存在着很强的正相关关系，即使在调整脂肪质量的情况下也是如此。脱脂质量是能量消耗的主要决定因素，24小时能量消耗也与能量摄入量密切相关。此外，即使在调整了无脂肪质量后，能量消耗的剩余仍然与能量摄入量有关。这表明能量需求的动态平衡感觉主要由代谢率决定，代谢率主要由脱脂质量驱动。 为了开发测量自由生活食物摄入量的方法，我们正在进行研究，验证使用我们的自动售货机的咀嚼和吞咽监测器。我们最初对10个个体进行的初步研究显示了一些积极的结果，但我们正在继续使用升级的咀嚼监测器，以更好地捕捉进食过程。 我们正在继续我们的研究，调查稳定同位素作为饮食模式的生物标志物。个人(n=40)将在3个月内根据肉类、苏打和鱼类含量的不同而食用不同的饮食，并将分析血浆、头发和脂肪组织样本中稳定同位素C13和N15的变化。我们还将调查这些饮食模式如何影响行为和表现测试、葡萄糖耐量和能量消耗。我们目前已经完成了13名志愿者在这项密集的研究中，这需要在我们的住院部停留14周。

Energy intake and dietary macronutrient composition is the most difficult part of the energy balance equation to measure. In a natural history study of factors which predict food intake and using an inpatient computerized vending machine system, food intake has been measured over 180 individuals. In individuals undergoing the study more than once the intra-class correlation coefficient is very high (r=0.9) indicating that these studies although performed in an inpatient setting are very reproducible. This study has demonstrated that higher respiratory quotient, the ratio of carbohydrate oxidation to lipid oxidation which predicts weight gain, also predicts weight gain. The component of respiratory quotient which best predicted food intake was higher carbohydrate oxidation indicating a role for carbohydrate (likely glycogen) balance in the regulation of short term food intake. However, we did not find that glycogen depletion increased food intake in a follow-up study. As noted above respiratory quotient is a ratio of carbohydrate to lipid oxidation. Central hypothalamic long chain fatty acid signaling can affect both food intake and peripheral lipid oxidation. Thus, we are planning future studies which investigate the role of these fatty acids in controlling food intake. In particular, we are developing a study which investigates nasal administration of a long chain fatty acid with subsequent measurement of food intake. We have also demonstrated that one of the most important determinants of food intake is fat free mass. There is a strong positive association between fat free mass (adjusted for height) and food intake, which persists even when adjusted for fat mass. Fat free mass is the major determinant of energy expenditure, and 24 hour energy expenditure is also strongly associated with energy intake. Furthermore, even after adjustment for fat free mass, the residual of energy expenditure was still associated with energy intake. This indicates homeostatic sensing of energy needs is determined primarily by metabolic rate which is driven largely by fat free mass. To develop methods to measure free living food intake, we have ongoing studies which are validating chewing and swallowing monitors using our automated vending machines. Our initial pilot study of ten individuals demonstrated some positive results, but we are continuing with an upgraded chewing monitor to better capture eating episodes. We are continuing our study investigating stable isotopes as biomarkers for dietary patterns. Individuals (n=40) will consume diets over 3 months which vary by meat, soda and fish content and plasma, hair, and adipose tissue samples will be analyzed for changes in the stable isotopes C13 and N15. We will also investigate how these dietary patterns affect behavioral and performance testing, glucose tolerance and energy expenditure. We have currently completed 13 volunteers in this intensive study which requires a 14 week stay on our inpatient unit.