PROTEIN-SPARING MODIFIED FAST IN PROMOTING WEIGHT LOSS IN SEVERELY OBESE ADOLES

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。在过去的二十年里，儿童肥胖症在美国和其他工业化国家已经达到了流行病的程度。除了众所周知的共病医疗条件，临床抑郁症已被证明在一些青少年的研究与肥胖以及在OB基因产生瘦素的遗传变异。仅在美国就有大约600万超重儿童迫切需要有效的治疗策略。生酮饮食，如蛋白质节约改良快速（PSMF），在新闻界和最初的科学研究中都被认为是一种安全有效的成年人短期减肥方法。对儿童的研究有限，这种饮食的代谢机制也知之甚少。本研究的目的是比较PSMF饮食与低脂肪、低热量（LFLC）饮食在肥胖青少年中促进体重指数降低、脂质和碳水化合物代谢改善、体脂减少以及抑郁和情绪指标改善的疗效。另一个目的是检查锌摄入量，锌状态和胰岛素水平的相互关系。共有50例年龄在12至18岁之间的原发性肥胖（定义为年龄的BMI第97百分位数）受试者（男性和女性）将随机接受为期12周的PSMF或LFLC饮食，以及规定的运动计划。所有患者都将接受基线研究以及监督饮食的开始。随访的变量将包括量热法结果、体重、身高、双能X线吸收测定法（DEXA）、儿童抑郁量表（CDI）评分、肝脏特征、血脂特征、胰岛素、胰岛素样生长因子-1、游离脂肪酸、瘦素、甘油和b-羟基丁酸水平以及锌状态标志物。12周后，受试者将过渡到维持饮食，并在6个月和9个月时进行随访测试。我们还建议招募另外20名正常体重的青少年对照受试者，以确定与正常体重的青少年相比，肥胖青少年的C反应蛋白（CRP）是否升高，血浆锌和金属硫蛋白（MT）-mRNA是否降低（BMI为年龄第10至第75百分位数）。这些体重正常的对照组患者将仅接受一次门诊GCRC访视，以进行身高和体重测量以及单次抽血。我们预计，这项研究的结果将提供更深入的了解与PSMF饮食发生的代谢和行为变化，并导致体重减轻。

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. Childhood obesity has reached epidemic proportions in the US and other industrialized nations over the past twenty years. In addition to the well-known co-morbid medical conditions, clinical depression has been shown in some adolescent studies to be associated with obesity as well as genetic variations in the OB gene that produces leptin. Effective treatment strategies for the estimated six million overweight children in the US alone are desperately needed. Ketogenic diets, such as the protein sparing modified fast (PSMF) have been purported both in the lay press and in initial scientific studies to be a safe and effective method of obtaining short-term weight loss in adults. Studies in children have been limited and the metabolic mechanisms by which this diet works are poorly understood. The objectives of this study are to compare the efficacy of the PSMF diet to a low fat, low calorie (LFLC) diet in obese adolescents in promoting decreases in body mass index, improvements in lipid and carbohydrate metabolism, loss of body fat and improvement in measures of depression and mood. An additional objective is to examine interrelationships of zinc intake, zinc status, and insulin levels. A total of 50 subjects, both male and female, between the ages of 12 and 18 years, with primary obesity (defined as a BMI 97th percentile for age) will be randomized to receive a 12-week course of either PSMF or LFLC diet, in addition to a prescribed exercise program. All patients will be admitted for baseline studies as well as supervised initiation of the diet. Variables to be followed will include calorimetry results, weight, height, dual-energy x-ray absorptiometry (DEXA), Childhood Depression Inventory (CDI) scores, liver profile, lipid profile, insulin, insulin-like growth factor-1, free fatty acids, leptin, glycerol and b-hydroxybutyrate levels, and markers of zinc status. After 12 weeks, subjects will be transitioned to maintenance diets and follow-up testing will be done at six and nine months. We also propose to enlist an additional 20 normal weight adolescent control subjects to determine if C-reactive protein (CRP) is elevated and plasma zinc and metallothionein (MT)-mRNA is reduced in obese adolescents compared to normal weight adolescents (BMI for age 10th to 75th percentile). These normal weight controls will only have one visit to the outpatient GCRC for height and weight measurements and a single blood draw. We anticipate that the findings of this study will offer greater insight into the metabolic and behavioral changes that occur with the PSMF diet and result in weight reduction.