GROWTH HORMONE AS A DETERMINANT OF WEIGHT REGULATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 随着肥胖率的惊人增长，找出导致个人体重增加的因素至关重要。即使卡路里摄入量和体力活动水平得到很好的控制，体重增加的易感性也是不同的。基础代谢率(BMR)代表了正常成年人每日能量消耗的最大部分，因此，个体间基础代谢率的变异性可能是决定体重增加易感性的主要因素。然而，导致基础代谢率和体重增加抵抗的因素尚不清楚。我们的初步数据表明，正常生长激素(GH)浓度高与大鼠在喂养过量时对体重增加的抵抗有关，而在人类喂养不足时与体重减轻程度更大有关。此外，我们还发现生长激素分泌的脉动性对几个代谢过程有深远的影响。因此，这些发现提示内源性GH分泌与体重调节有关，GH分泌的脉动性(峰值幅度)而不是GH的绝对浓度本身可能对这种影响起作用。由于生长激素影响了许多促成BMR的关键代谢过程(例如，蛋白质合成、蛋白质分解、底物循环)，我们预计GH浓度升高的人对体重增加的抵抗力将与由于这些过程中的部分或全部加速而导致的BMR增加有关。我们的总体假设是，生长激素分泌增加可以防止体重增加，这是由于导致BMR的主要代谢过程增加所致。找出容易导致个人体重增加的因素，将有助于建立更好的方法来降低肥胖率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With the alarming increase in the prevalence of obesity, identifying factors that predispose individuals to weight-gain is of critical importance. Even when caloric intake and physical activity levels are well controlled, susceptibility for weight-gain is heterogeneous. Basal metabolic rate (BMR) represents the largest portion of daily energy expenditure in normal adults, and as such, variability in BMR among individuals can be a major factor in determining the susceptibility for gaining weight. However, factors responsible for this variability in BMR and resistance to weight-gain remain unclear. Our preliminary data indicate that high-normal growth hormone (GH) concentration is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. In addition, we have found that the pulsatility of GH secretion has profound effects on several metabolic processes. Therefore, together these findings suggest that endogenous GH secretion is associated with body weight regulation, and the pulsatility (peak amplitude) of GH secretion, rather than the absolute GH concentration, per se, may be responsible for this effect. Because GH influences many of the key metabolic processes that contribute to BMR (e.g.; protein synthesis, proteolysis, substrate cycling), we anticipate that the resistance to weight-gain in persons with elevated GH concentrations will be associated with an increase in BMR due to acceleration of some or all of these processes. Our overall hypothesis is that increased GH secretion can protect against weight-gain due to an augmentation of major metabolic processes that contribute to BMR. Identifying factors responsible for predisposing individuals to weight-gain will lead to establishing improved methods for reducing the prevalence of obesity.'