Project Number: 6250-51000-046-00
Start Date: May 21, 2004
End Date: Mar 30, 2009
1) A systemic genomic scan and follow-up fine mapping and sequencing of positional candidate genes will be performed on 300 overweight Hispanic children and their biological parents and siblings with respect to adiposity, the regulation of food intake, energy expenditure and energy partitioning before and after weight loss. 2) A 5-level body composition model will be determined from multiple-method body composition assessments in 1500 multi-ethnic children. The predictive accuracy of the model for the individual will be verified by longitudinal restudy. 3) Implement an intensive physical activity intervention in urban African- and Mexican-American families that will assist in determining specific barriers/facilitators for children and families adhering to the physical activity component of the 2005 Dietary Guidelines. 4) Animal models (murine) and human tissue will be used to characterize myeloid and lymphoid cells within adipose tissue and changes that occur in mice fed high fat diets. Phenotypic markers and in situ hybridization will be used to characterize the cell types, ultrastructural studies, and confocal microscopy will define the position of these cells in relationship to other structural components of the adipose tissue, and tissue fractionation techniques will be used to isolate these cells for function studies in vitro. Cell lines (e.g., RAW cells and 3T3 cells) will be used to study cytokine, chemokine and hormone release, adipocyte differentiation and lipid metabolism. Contributions of the immune cells to lipid metabolism in vivo will be sought in mice with disrupted or activated (e.g., with endotoxin) immune cell functions. 5) Insulin sensitivity and secretion will be studied using stable isotopes, and intramyocellular and intrahepatic fat content will be determined using MRI. 6) Through employing both hypothesis-generating and hypothesis-testing approaches to ascribe roles for the circadian clock within the adipocyte will increase our understanding of altered sleep patterns and how they may contribute to the accumulation of body fat.