Project Number: 6251-51000-007-00
Project Type: Appropriated

Start Date: Apr 01, 2009
End Date: Mar 31, 2014

Objective:
Dietary factors may significantly impact long-term human health during adult life as a result of the influences on early developmental events. Certain common dietary factors appear to be capable of affecting growth and development; transiently and permanently altering metabolism; influencing body composition; and 4) preventing some diseases. For example, fruits, vegetables, grains, and milk contain natural compounds (phytochemicals, peptides, and proteins) that can alter development, physiology, and metabolism, which can ultimately lead to disease prevention and phenotypic changes. Additionally isoflavones are particularly concentrated in soybeans and can have many of the same actions as the major female hormones in women, the estrogens. Countries with regular consumption of large amounts of soy foods report lower incidence of cancer, cardiovascular disease, and obesity; and factors in soy (isoflavones and peptides) are postulated as being partially responsible. The objectives of our research include: 1) determine the effects of diet and physical activity in humans and animal models on development and organ function; 2) determine how early exposure to soy proteins and fruits confers resistance to chronic diseases such as mammary cancer, cardiovascular disease, and type 2 diabetes in later adult life; 3) evaluate multiple molecular mechanisms and identify bioactive components for chronic disease prevention by diets using appropriate models as measured by tumor suppressors and oncogenes; oxidative modification; inflammation; immunomodulation; and insulin sensitivity; 4) examine consequences of early intake of combinations of foods (soy, fruits) on chronic disease prevention, organ development and signaling pathways, relative to dietary intake of a single food; 5) investigate the mechanisms of maternal obesity-induced fetal programming; 6) examine the impact of type and amount of dietary macronutrient components on development of obesity and associated metabolic sequelae in an animal model of pediatric total enteral nutrition and in clinical studies; and 7) identify the potential of dietary factors for mitigating risk of obesity via nutritional programming. It is essential to ascertain the long-term health consequences, both positive and negative, of early consumption of these phytochemicals since it may impact a major segment of our American population.

Approach:
Studies will focus on the various dietary factors found in foods commonly consumed by children, such as fruits, rice, 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 chronic diseases by altering tissue differentiation, inflammation, and/or oxidative status. We will use rodent models to mechanistically address the molecular and cellular pathways regulated by dietary intake of soy protein isolates and berries in mammary tissue, aorta, liver, pancreas, and skeletal muscle; 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 from birth to age 6 years, The Beginnings Study. Breast-fed, milk formula-fed, and soy formula-fed children are studied for growth, development, body composition, and metabolism. In addition, bone development, and immune system development and function will be studied in children, and animal models will be utilized to explore molecular mechanisms underlying the effects of early dietary exposures. The rat model will be used to understand the parental genetic transmission of the susceptibility to high fat feeding to future generations and underlying molecular, biochemical, and endocrine mechanisms, in the offspring.