Location: Arkansas Children's Nutrition Center
Project Number: 6026-51000-010-000-D
Project Type: In-House Appropriated
Start Date: Mar 23, 2014
End Date: Mar 3, 2019
Overall objective is to gather evidence about important environmental factors that have long-term consequences on child development/health, and their health as children become adults. 1: Continue Beginnings study, longitudinal study of growth/development/body composition in infants breast-fed or fed soy/cow milk formula. 2: Determine if soy feeding affects estrogen receptor beta using chromatin immunoprecipitation analysis; gene deletion studies in appropriate animal models to ascertain if soy protein affects reproductive development/metabolism/body composition via activation of ERbeta-mediated signaling. 3: Determine body composition/metabolism of prepubertal pigs fed breast milk/milk formula/soy formula as neonates, then weaned onto either low or high fat diet. Compare data with body composition/metabolism in children age 5 from Beginnings Study. 4: Determine effects of early diet in pig model on gut-associated lymphoid tissue development/function; ... 5: Characterize effects of neonatal diet on composition of intestinal microbiota, Collect urine/fecal samples from Beginnings Study infants/children at 3/6/9/12 months and yearly thereafter. 6: Determine if feeding blueberries (BB) and other fruits/vegetables containing phenolic acid (PA) chlorogenic acid (CA) or treatment with CA metabolite hippuric acid stimulate bone growth in rodent model; examine role of G-coupled receptor protein GPR109A as potential mediator of PA effects on bone. 7: Perform peripheral quantitative computerized tomography to study bone morphology; measure urine/serum bone turnover markers in lean/obese prepubertal children with/without additional symptoms of insulin resistance. 8: Determine ability of diets containing BB to block obesity-induced impairment in bone quality/strength in weaning rats; determine method of activation in underlying mechanisms by which this occurs. Determine if bone turnover markers in urine/serum of obese children are improved after short-term intervention with BB-containing diets. 9: Determine if toll-like receptor/early response protein-1 signaling is mediating embryonic/placental inflammation and epigenetic dysregulation in offspring due to maternal obesity in rodent models/human subjects. 10: Characterize effect of maternal obesity on programming offspring's metabolism and risk of obesity later in life in the Glowing study. 11: Determine if interventions prior to/during pregnancy that alter maternal hyperinsulinemia, gastrointestinal microbiome and/or inflammation prevent obesity-induced metabolic programming in animal models. 12: Determine if reprogramming of offspring energy metabolism/mitochondrial function can occur by promoting neonatal physical activity or dietary factors in rodent models. 13: Determine effects of early diet on neurocognitive development by completing neurophysiological/behavioral aspects of Beginnings study. 14: Determine effects of diet composition, meal pattern/frequency on brain development/function, and behavioral dynamics important for learning in well-characterized lean/obese school children. 15: Characterize how neurocognitive functions associated with obesity can be improved by physical activity.
Studies will focus on the various dietary factors found in foods commonly consumed by children, such as breast milk, infant formulas, fruits, grain, milk, and soy to determine their long-term health effects in infants and children. We will analyze how the early exposure to protein sources and fruits normally consumed by infants and children prevents the initiation of and protects against development of chronic diseases by altering tissue differentiation, inflammation, and/or oxidative status. We will use animal models to mechanistically address the molecular and cellular pathways regulated by intake of various dietary factors (such as in soy foods, berries, grains and milk) in mammary tissue, liver, adipose tissue, pancreas, gastrointestinal tract, bone, skeletal muscle and the immune system; identify tissue and serum biomarkers of healthy status associated with these diets; and provide new molecular targets and processes underlying chronic diseases that may be influenced by proper nutrition. Additional work will be undertaken in an observational study of infants, The Beginnings Study, which is a longitudinal study of breast-fed, milk formula-fed, and soy formula-fed children from birth through puberty, will evaluate growth, development, body composition, metabolism, bone development, and immune system development and function. Animal models such as the neonatal pig will be utilized to explore molecular mechanisms underlying the effects of early dietary exposures. Rodent models will be used to understand the parental epigenetic transmission of the effects of maternal obesity and high fat feeding to future generations and underlying molecular, biochemical, and endocrine mechanisms, in the offspring. These studies will be translated in an ongoing longitudinal clinical study of infant body composition in children of lean and overweight women (The Glowing Study). Work will be accomplished by evaluating critical periods of development and vulnerable stages of life (i.e. the nutritional status of women at the moment of conception; nutritional and developmental issues during pregnancy and lactation). Children (infants, toddlers, and school-aged youths) will be studied to evaluate the effects of infant diet (specifically, breast-milk and a variety of infant formulas) on morphological, neurophysiological, behavioral, and cognitive development in infants and children. Nutritional status assessments, anthropometric measurements, body composition, energy metabolism, physical activity fitness, urine and blood analysis, and measures of brain structure (MRI imaging), psychological and behavioral status (standardized testing), neuropsychological, and cognitive measures will be obtained and analyzed. The effects of diet composition, meal patterns, meal frequency, physical activity, and body composition on brain function, behavioral dynamics, learning, and school performance will be assessed in normal weight and overweight/obese school children using validated survey instruments and state-ofthe-art research equipment.