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）：即使热量摄入量和体育锻炼受到良好的控制，体重增加的敏感性也很大。由于基础代谢率（BMR）约占每日能量消耗总数（TDEE）的70％，因此即使是BMR的较小差异也会影响每日能量平衡，从而增加了增加体重的敏感性。我们的初步数据表明，高正常生长激素（GH）的分泌与人体过度饮食时对大鼠体重增强的耐药性有关，而在人类不足时的体重则更大。鉴于GH会影响导致BMR的许多关键代谢过程，因此我们假设具有高正常GH的人会因这些过程加速速率而产生的高正常GH的人会抵抗体重增加。我们将在106个非肥胖男性和女性中测量基底24H GH分泌和BMR。我们还将测量蛋白质合成，蛋白水解，甘油三酸酯/脂肪酸循环（所有使用稳定的同位素示踪剂方法测量），以确定这些过程之间的关系，BMR和GH [特定目标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这些群体之间的腹腔内肥胖在其GH分泌方面明显不同（饮食前测量的GH）[特定目标2]。正常GH的受试者的一部分将在2周过喂养期间接受静脉内GH，以恒定的速率或2。作为脉冲输注（模仿内源性分泌）。将每天评估BMR，并在2 WKS结束时测量蛋白质合成，蛋白水解和甘油三酸酯/脂肪酸循环[特定AIM 3]。我们预计，较高的GH脉动性（峰值振幅），而不是GH浓度升高，本身会增加蛋白质合成，蛋白水解和甘油三酸酯/脂肪酸循环，从而增加BMR的增加和对体重增加的抗性。识别负责使个体体重增强的因素将有助于打击肥胖症患病率的令人震惊的上升。