Phenotypic and metabolic characteristics in early childhood leading to obesity

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 DESCRIPTION (provided by applicant): According to the Centers for Disease Control and Prevention, 23.8 percent of children age 2 to 5 years are overweight and 11.1 percent are obese. Studies have demonstrated that children who become obese as early as age 2 years are more likely to be obese as adults. Accordingly, 1 in 4 children is at risk for developing obesity later in life in the United States. Weight velocity during infancy has been associated with later risk of obesity in numerous studies. However, most studies have reported on anthropometric rather than body fat mass measures. It is unknown which patterns of fat mass and fat free mass accretion during the first two years of life yield obesity development. Similarly, very few studies have investigated fat mass distribution in infants and children especially during a period of rapid growth and increased energy needs. Our preliminary analyses suggest that while maternal BMI and energy intake contribute to the association between weight velocity and overweight/obese status at age 2 years, there are likely other factors that lead to greater weight velocity in infany. We postulate that weight velocity is also driven by a shift in metabolism such that infants who will become overweight or obese develop an energy sparing phenotype leading to greater weight gain compared to infants who remain normal weight during childhood. Therefore they are more efficient at storing excess calories leading to increased accumulation of fat mass. Though this has not been studied in humans and no data exist to suggest how this might influence various fat depots, this energy sparing phenotype is supported by animal models demonstrating that maternal obesity programs offspring metabolism in utero resulting in decreased energy expenditure and fatty acid oxidation rates. The objective of this application is to address these gaps in knowledge by measuring energy intake, total energy expenditure rates, fatty acid oxidation rates, and fat mass accretion and distribution of infants and children during the first two years of life while controlling for important confounding factors. We will test the hypothesis that excessive weight gain during infancy is driven by both greater energy intake and lower energy expenditure and fatty acid oxidation rates, resulting in greater fat mass accretion. The first aim will determine the associations between weight velocity, energy intake and energy expenditure of infants and children at age 6, 12 and 24 months. For this aim, total energy expenditure will be evaluated using doubly-labelled water. The second aim will determine the associations between weight velocity and fatty acid oxidation of infants and children using stable isotope techniques at age 6, 12 and 24 months. The third aim will evaluate fat mass accretion and distribution in infants and children during the first two years of life using dual energy X-ray absorptiometry and quantitative nuclear magnetic resonance techniques.