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United States Department of Agriculture

Agricultural Research Service

Related Topics


Location: Arkansas Children's Nutrition Center

2011 Annual Report

1a. Objectives (from AD-416)
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 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 this 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 sequence in an animal model of pediatric total enteral nutrition and in clinical studies; 7) identify the potential of dietary factors for mitigating risk of obesity via nutritional programming; and 8) determine the effects of genetic and epigenetic interactions with diet, nutritional status, weight gain, and behavior during gestation on placental and offspring development, health and susceptibility to chronic diseases, including obesity. 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.

1b. Approach (from AD-416)
Studies will focus on the various dietary factors found in foods commonly consumed by children, such as infant formula, 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 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, aorta, liver, adipose tissue, 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. 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) and the development of eating behaviors during childhood, adolescence, and later stages of life.

3. Progress Report
Studies occurred in pregnant women and rodents, human and animal placentas, and infants/children, and were translational, clinical, or basic in nature, aimed at learning how diet, nutritional status, and dietary factors affect normal child development and disease prevention. We began translational/clinical studies to translate the animal findings to human subjects and to determine how pregnant women permanently program the metabolism of their offspring that leads to obesity. Clinical studies conducted included: studies of the eggs (oocytes) from women of differing nutritional and body composition status (lean vs. obese); studies of pregnant women; and studies of placentas. These are longitudinal studies of early periods of life: just prior to or immediately after conception (peri-conceptional); during pregnancy; and infancy. We suspect that a large amount of childhood obesity is caused by maternal programming of offspring metabolism, and these studies test that hypothesis. In the Beginnings Study, we are comparing growth, development and body composition of breast-fed or formula-fed (milk-based or soy-based) children. Unique data is being generated on normal child development with these three infant diets. Basic studies include animal studies on the physiological and biochemical effects and gene expression patterns in liver, bone, and mammary gland associated with early feeding of soy protein isolate (SPI) (the protein component of soy infant formula), rice protein isolate (RPI) (widely used in processed foods), and blueberries. SPI and RPI were found to protect against metabolic syndrome. All diets were protective against development of cardiovascular disease which appears to be associated with antioxidant and anti-inflammatory actions. An important research area is related to "if soy is an estrogen". We found that none of the beneficial health effects of SPI act through estrogen-dependent mechanisms. Thus, soy foods are not acting like an estrogen. In fact, gene expression patterns in liver, bone, and mammary gland suggest little overlap between soy and estrogen profiles and anti-estrogenic effects when SPI feeding and estrogen treatment are combined. Blueberries appear to block inflammation and stimulate bone growth through the actions of phenolic acid metabolites of the berry pigments produced by the actions of gut bacteria. We developed a new rat model of pediatric obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) by overfeeding a high fat diet via total enteral nutrition during early development. Using rodent models of diseases, we found that soy prevents the unregulated growth of mammary epithelial cells that leads to breast cancer and defined mammary stem/progenitor cells as new targets of dietary factors for breast cancer protection. Consumption of blueberries was found to prevent mammary cancer and the mechanism may be through certain phenolic acids that appear in serum of mice fed blueberries. The ADODR monitors project activities by visits, review of purchases of equipment, review of ARS funded foreign travel, and review of ARS funds provided through the SCA.

4. Accomplishments

Last Modified: 10/18/2017
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