Growth hormone as a determinant of weight regulation

生长激素作为体重调节的决定因素

• 批准号: 7280885
• 负责人: Jeffrey F Horowitz
• 金额: $ 42.89万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7280885
• 关键词: Acceleration; Adult; Affect; Albumins; Appearance; Attenuated; Basal metabolic rate; Body Composition; Body Weight; Body Weight decreased; Body fat; Caloric Restriction; Daily; Data; Diet; Elevation; Energy Intake; Energy Metabolism; Fatty Acids; Fibrinogen; Hospitals; Human; Individual; Infusion procedures; Intra-abdominal; Intravenous; Lead; Leucine; Measures; Metabolism; Methods; Muscle Proteins; Non obese; Obesity; Persons; Physical activity; Physiologic pulse; Predisposing Factor; Predisposition; Prevalence; Process; Protein Biosynthesis; Proteolysis; Protocols documentation; Pulse taking; Rate; Rattus; Regulation; Research Personnel; Resistance; Somatotropin; Substrate Cycling; Tracer; Triglycerides; Week; Weight; Weight Gain; Woman; abdominal fat; day; energy balance; improved; men; programs; restricted physical activity; stable isotope

DESCRIPTION (provided by applicant): The susceptibility to gain weight is highly variable even when caloric intake and physical activity are well controlled. Because basal metabolic rate (BMR) represents approximately 70% of total daily energy expenditure (TDEE), even a small difference in BMR can affect daily energy balance, thereby increasing the susceptibility for gaining weight. Our preliminary data indicate that high-normal growth hormone (GH) secretion is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. Given that GH influences many of the key metabolic processes that contribute to BMR, we hypothesize that persons with high-normal GH will be resistant to weight gain because of a high BMR, resulting from accelerated rates of these processes. We will measure basal 24h GH secretion and BMR in 106 non-obese men and women. We will also measure protein synthesis, proteolysis, triglyceride/fatty acid cycling (all measured using stable isotope tracer methods) to determine the relationships among these processes, BMR, and GH [Specific Aim 1]. Subjects identified as having "low-normal" (<1.5 ug/L) and "high-normal" (>3 ug/L) 24h GH will then be admitted to the hospital for a 2 wk overfeeding protocol (approximately 2000 kcal/d >TDEE - with restricted physical activity), immediately followed by a 4 wk caloric restriction protocol (approximately 750 kcal/d <TDEE) to compare changes in weight, body composition and intra-abdominal adiposity between these groups that differ markedly in their GH secretion (GH measured before the diet) [Specific Aim 2]. A subset of subjects with low normal GH will receive intravenous GH throughout the 2 wk overfeeding period at either: 1. a constant rate or 2. as a pulsatile infusion (to mimic endogenous secretion). BMR will be assessed daily and protein synthesis, proteolysis, and triglyceride/fatty acid cycling will be measured at the end of the 2 wks [Specific Aim 3]. We anticipate that a higher GH pulsatility (peak amplitude), rather than elevated GH concentration, per se, will increase protein synthesis, proteolysis, and triglyceride/fatty acid cycling with a resultant increase in BMR and resistance to weight-gain. Identifying factors responsible for predisposing individuals to weight-gain will help combat the alarming rise in the prevalence of obesity.

描述（由申请人提供）：即使热量摄入和体力活动得到很好的控制，体重增加的敏感性也有很大差异。由于基础代谢率 (BMR) 约占每日总能量消耗 (TDEE) 的 70%，因此即使 BMR 的微小差异也会影响每日能量平衡，从而增加体重增加的可能性。我们的初步数据表明，正常高水平的生长激素（GH）分泌与大鼠在进食过量时抵抗体重增加有关，而在人类进食不足时则与体重减轻更大有关。鉴于 GH 影响许多有助于 BMR 的关键代谢过程，我们假设 GH 正常值较高的人将因这些过程加速而导致 BMR 高，从而抵抗体重增加。我们将测量 106 名非肥胖男性和女性的基础 24 小时 GH 分泌和 BMR。我们还将测量蛋白质合成、蛋白水解、甘油三酯/脂肪酸循环（全部使用稳定同位素示踪剂方法测量），以确定这些过程、BMR 和 GH 之间的关系 [具体目标 1]。被确定为“低正常”（<1.5 ug/L）和“高正常”（>3 ug/L）24 小时 GH 的受试者将入院接受为期 2 周的过度喂养方案（约 2000 kcal/d） >TDEE - 限制体力活动），然后立即进行 4 周热量限制方案（约 750 kcal/d <TDEE），以比较这些组之间的体重、身体成分和腹内肥胖情况在 GH 分泌方面存在显着差异（饮食前测量 GH）[具体目标 2]。一部分正常 GH 较低的受试者将在整个 2 周的过度喂养期间接受静脉 GH：1. 恒定速率或 2. 作为脉冲输注（以模拟内源性分泌）。每日评估 BMR，并在 2 周结束时测量蛋白质合成、蛋白水解和甘油三酯/脂肪酸循环 [具体目标 3]。我们预计，更高的 GH 脉动（峰值幅度），而不是升高的 GH 浓度本身，将增加蛋白质合成、蛋白水解和甘油三酯/脂肪酸循环，从而增加 BMR 和体重增加的阻力。找出导致个体体重增加的因素将有助于对抗肥胖流行率的惊人上升。