Project Number: 6250-51000-046-02
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2005
End Date: Sep 30, 2010

Objective:
The objective of this cooperative research is to identify a number of genes that affect the expression of childhood obesity in Hispanic children; establish a reference model of body composition in children; understand the barriers and facilitators to the physcial activity guildelines of the 2005 Dietary Guidelines for Americans; determine the contribution of leukocytes to the composition and function of adipose tissue; determine whether a 12-week exercise program without intent to weight loss would increase insulin sensitivity and reduce insulin secretion and glucose production from gluconeogenesis in obese adolescents; and to test the efficacy of an after-school physical activity program that meets the Healthy People 2010 guidelines for lowering body fat, increasing activity energy expenditure and physical activity level in Hispanic children. 1)Genetic and Environmental factors Contributing to Childhood Obesity - Identify a number of genes that affect the expression of childhood obesity in Hispanic children. 2) Biological Diversity of Human Growth: Body Composition Reference Standards for Children - Develop a greater understanding of the changes in body composition starting in infancy, using multiple, independent assays for bone, muscle, water, and body fat content. 3) Barriers and Facilitators to the Physical Activity Guidelines of the 2005 Dietary Guidelines for Americans - identify what environmental and/or personal factors will be necessary for most Americans to adhere to these recommendations. 4) Nutritional Influences on Innate Immunity - Study two aspects of the innate immune system in a mouse model of dietary induced obesity as there is increasing interest in the effects of obesity on components of the innate immune system with regard to its role in host resistance to infection and its capacity to cause tissue injury. 5) Effects of Ethnicity, Exercise and Obesity on Glucose Metabolism and Insulin Sensitivity in Healthy Adolescents - Increase our understanding of the metabolic effects of ethnicity, exercise and obesity in adolescents and possibly identify factors, which may increase the risk of type 2 diabetes and design new treatment strategies to prevent or delay the development of type 2-diabetes in adolescents. 6) Circadian Clocks in Adipose Biology and Obesity - is to maintain a greater understanding that altered sleep patterns associated with our "24-hour" lifestyle may contribute to the accumulation of body fat, and that such altered sleep patterns may ultimately represent alterations in both the central and peripheral circadian clock mechanisms.

Approach:
1) Genetic and Environmental factors Contributing to Childhood Obesity - Perform a genome scan to identify loci that influence quantitative phenotypes related to adiposity, the regulation of food intake, energy expenditure, and energy partitioning in children. Phenotyping of the children will occur which includes anthropometry, body composition, food intake, eating behavior, energy expenditure, fitness, and physical activity, and metabolites, hormones and cytokines involved in energy homeostasis. Weight changes after initial phenotyping and after a weight loss intervention will be measured to determine if weight changes and the metabolic, hormonal and immunologic responses to weight changes are dependent upon genotype. 2) Biological Diversity of Human Growth: Body Composition Reference Standards for Children - Determining the normal biological diversity during growth among different ethnic groups (European-, African-, and Mexican-American). From these data, a multi-level Reference Model of Pediatric Body Composition will be established using LMS statistical modeling techniques. Quantitative indices will be developed to identify infants and young children with abnormal body composition most often associated with increased risk for chronic adulthood diseases. Development of unique and innovative in vivo assays specific to the pediatric population will be established. 3) Barriers and Facilitators to the Physical Activity Guidelines of the 2005 Dietary Guidelines for Americans - implementing an intensive physical activity intervention in African and Mexican American families that will assist in determining specific barriers/facilitators for African and Mexican American children and families adhering to the 2005 physical activity Dietary Guidelines. 4) Nutritional Influences on Innate Immunity - Analyze the accumulation and potential functions of leukocytes in adipose tissue, and the accumulation and capacity for injury of leukocytes in the liver. 5) Effects of Ethnicity, Exercise and Obesity on Glucose Metabolism and Insulin Sensitivity in Healthy Adolescents - Study 96 adolescents on three occasions using state of the art stable isotope and magnetic resonance imaging (MRI) techniques. 6) Circadian Clocks in Adipose Biology and Obesity - employ both hypothesis-generating and hypothesis-testing approaches to ascribe roles for the circadian clock within the adipocyte.