Location: Children's Nutrition Research Center
Project Number: 3092-10700-070-000-D
Project Type: In-House Appropriated
Start Date: Mar 4, 2024
End Date: Mar 3, 2029
Objective:
Researchers will 1) determine the immune protective function of human milk and bovine colostrum-derived immunoglobulin A and protection against necrotizing enterocolitis (NEC) in a formula-fed, preterm pig model; 2) determine the impact of citrulline and arginine supplementation on metabolism and prevention of NEC incidence in formula-fed preterm pigs; 3) determine the nutritional regulation of muscle growth following preterm birth and develop targeted amino acid supplementation to promote lean growth and optimal development; 4) determine the optimum bioavailability of different chemical forms of choline that maximize the plasma and tissue deposition and function of long chain fatty acids in preterm pigs; 5) determine the impact of a maternal high-fat diet on the development of thermogenic adipocytes in the offspring; 6) define how early-life transient overexpression of gap junction protein Connexin43 slows fat accretion when mice are fed a high-fat diet in adulthood; 7) define the critical window when gut microbial exposure shapes the epigenetic regulation of intestinal stem cell function; and 8) determine the impact of perinatal nutrition and exercise on cardiovascular development and health.
Approach:
This research will be accomplished using a variety of models and scientific studies. Researchers will use neonatal piglet models to determine the extent to which the anabolic resistance to nutrition contributes to reduced muscle growth in the preterm and whether targeted amino acid supplementation will promote lean growth. We will determine the immune protective function of human milk and bovine colostrum-derived immunoglobulin A (IgA) and protection against necrotizing enterocolitis (NEC) in the preterm. We will determine the optimum bioavailability of different chemical forms of choline that maximize the plasma and tissue deposition and function of long chain fatty acids in the preterm. We will use mouse models to study the direct contribution of maternal high-fat diet to the development of thermogenic adipocytes in offspring and identify the underlying transcriptional regulators. We will investigate how a gap junction protein Connexin43 affects the gene expression by epigenetic mechanisms and whether an early-life intervention on adipocytes can reprogram fat deposition, energy balance, and glucose and lipid metabolism in adulthood. We will utilize germ-free mice and gut microbiota transplant experiments to delineate epigenetic cross-talks between gut microbiome and intestinal stem cells at distinct developmental stages. We will also use mouse models to understand the relationship between diet in early life and the risk for developing cardiovascular dysfunction, and how these differ between sexes.
