ROLE OF LIPOLYSIS IN HUMAN OBESITY AND FASTING

第二次全国健康与营养检查调查发现， 20-75岁的美国成年人中，约有3400万人肥胖 （大于理想体重的120%）。 然而，尽管高 肥胖症的流行以及与此相关的此类疾病风险的增加 作为糖尿病和高脂血症，目前尚不清楚是否健康风险， 肥胖仅仅是过量脂肪组织的功能， 肥胖者的脂肪组织调节是否也有缺陷。 脂肪的假定生理作用是提供一种替代燃料 在缺乏热量的时期。 造成这种情况的因素 禁食期间脂肪分解的加速尚不完全清楚，但 它们可能是荷尔蒙、神经和新陈代谢的结合 影响。 初步信息表明，禁食的肥胖者 保护免受脂解的过度刺激， 身体消耗游离脂肪酸的能力，可能会形成 荷尔蒙环境的改变 拟议的实验将检查胰岛素对 脂肪分解、游离脂肪酸再酯化和脂肪氧化 非糖尿病志愿者，以确定是否脂肪异常 糖代谢异常可以解释糖代谢引起的胰岛素抵抗。 接下来的一系列实验将评估控制 脂肪分解，以及脂肪分解与葡萄糖稳态和 蛋白质保存，在过夜和三天禁食瘦和肥胖 非糖尿病志愿者 这些实验将监测 脂质、葡萄糖和蛋白质周转的选择性清除或阻断 已知影响脂质代谢的激素、神经或代谢因素。 倒数第二个实验将研究是否增强 肥胖者禁食期间的脂解由于以下原因而受损： 减少激素刺激，如果是这样，是否更换 激素缺乏，最有可能是生长激素，可以加速脂肪分解 而不会对新陈代谢产生不良影响。 如果是这样，最终 实验将评估慢性生长激素治疗对 脂肪、蛋白质和碳水化合物的代谢 低热量饮食。

The second National Health and Nutrition Examination survey found that 26% of U.S. adults, or about 34 million people, aged 20-75 years were obese (greater than 120% ideal body weight). However, despite the high prevalence of obesity and the associated increased risk of such conditions as diabetes and hyperlipidemia, it is not known whether the health risks of obesity are simply a function of the excessive amount of adipose tissue or whether regulation of adipose tissue is also defective in obese persons. The presumed physiological role of fat is to provide an alternative fuel during periods of caloric deprivation. The factors responsible for acceleration of lipolysis during fasting are incompletely understood, but they are presumably a combination of hormonal, neural and metabolic influences. Preliminary information suggests that fasted obese persons are protected against excessive stimulation of lipolysis and overwhelming of the bodies capacity to consume free fatty acids, possibly form an alteration in the hormonal milieu. The proposed experiments will examine the regulation by insulin of lipolysis, FFA reesterification and fat oxidation in lean nd obese nondiabetic volunteers, to determine whether abnormalities of fat metabolism could explain the insulin resistance of carbohydrate metabolism. The next series of experiments will evaluate the factors that control lipolysis, and the relationship of lipolysis to glucose homeostasis and protein conservation, in overnight and three day fasted lean and obese nondiabetic volunteers. These experiments will monitor the effect of lipid, glucose and protein turnover of selective removal or blockade of hormonal, neural or metabolic factors know to influence lipid metabolism. The penultimate experiments will investigate whether enhancement of lipolysis during fasting is impaired in obese persons as a result of reduced hormonal stimulation and, if so, whether replacement of the hormonal deficiency, most likely growth hormone, can accelerate lipolysis without untoward metabolic consequences. If this is the case, the final experiment will evaluate the effect of chronic growth hormone treatment on fat, protein and carbohydrate metabolism in obese subjects consuming a hypocaloric diet.