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.
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