METABOLIC ADAPTATIONS OF OBESITY WITH GH ADMINISTRATION

GH 给药对肥胖的代谢适应

• 批准号: 7376586
• 负责人: ARIEL Lev BARKAN
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376586
• 关键词: fats; glucose; lipolysis; metabolism; muscle; obesity; proteins; role; secretion; somatotropin; tissues

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. In the United States, the prevalence of obesity has reached alarming and even epidemic proportions. Despite the billions of dollars spent annually on weight-loss related products more than 50 million Americans are either overweight or obese. Growth hormone (GH) and insulin are primary regulators of protein synthesis, as well as lipid and glucose metabolism. Serum GH is reduced in obese subjects primarily as a result of reduced GH pulse amplitude. Thus, GH secretion in obese individuals is not only decreased in absolute terms but the pattern of GH presentation to the peripheral tissues is changed from a highly pulsatile one to absence of pulsatile GH secretion, i.e resembling a low rate constant infusion. The pattern of GH secretion has been shown to be an independent factor in the regulation of liver and bone metabolism. Thus a similar role of GH pulsatility may also be of importance of regulating energy distribution whereby different patterns of GH presentation to the peripheral tissues playing divergent roles in selective metabolic activities of fat and protein. The impairment in GH secretion is due to the excess of visceral fat. It is not clear whether administration of GH will increase lipolytic(breakdown of fat) rate or whether mode of administration of GH alters lipolysis. A single infusion of GH stimulates muscle protein synthesis, whereas more prolonged administration reduces urinary urea excretion and increases whole body protein synthesis. Administration of GH diminishes protein breakdown and promotes lean body mass with time. We propose to study whether giving Growth hormone as continuous vs. pulsatile infusion will have differential effects on protein synthesis, lipolysis, glucose uptake and insulin sensitivity involved in regulating fuel metabolism in muscle. We will study 24 obese subjects. They will be admitted to GCRC for 9 days in total over 2 visits. They will be studied with special metabolic tests during continuous or pulsatile GH infusion administration . The effects on metabolism will be evaluated by blood tests following infusions of fat, glucose and protein and response of muscles will be evaluated with muscle biopsy. The results of this study will pave the way for better understanding of the role of GH in metabolic adaptation in obese subje

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在美国，肥胖症的流行已经达到了令人担忧的甚至是流行病的程度。尽管每年花费数十亿美元用于减肥相关产品，但仍有5000多万美国人超重或肥胖。生长激素（GH）和胰岛素是蛋白质合成以及脂质和葡萄糖代谢的主要调节剂。肥胖受试者的血清GH降低主要是由于GH脉冲幅度降低。因此，肥胖个体的GH分泌不仅在绝对值上减少，而且GH呈递到外周组织的模式从高度脉动型改变为缺乏脉动型GH分泌，即类似于低速恒定输注。GH分泌模式已被证明是调节肝脏和骨代谢的独立因素。因此，GH脉动性的类似作用也可能对调节能量分布具有重要意义，从而GH向外周组织的不同模式在脂肪和蛋白质的选择性代谢活动中发挥不同的作用。生长激素分泌的障碍是由于内脏脂肪过多。目前尚不清楚GH的给药是否会增加脂解（脂肪分解）率或GH的给药方式是否会改变脂解。单次输注GH刺激肌肉蛋白质合成，而更长时间的给药减少尿尿素排泄并增加全身蛋白质合成。生长激素的管理减少蛋白质分解，并促进瘦体重随着时间的推移。我们建议研究是否给予生长激素作为连续与脉冲输注将有不同的影响蛋白质合成，脂解，葡萄糖摄取和胰岛素敏感性参与调节肌肉中的燃料代谢。我们将研究24名肥胖受试者。他们将在2次访视中进入GCRC共9天。在连续或脉冲GH输注给药期间，将采用特殊代谢试验对其进行研究。将通过输注脂肪、葡萄糖和蛋白质后的血液检查评价对代谢的影响，并通过肌肉活检评价肌肉的反应。本研究结果将为更好地理解GH在肥胖受试者代谢适应中的作用铺平道路。