NUTRITION AND INTESTINAL DEVELOPMENT AS REGULATORS OF HEALTH PROTEIN ANABOLISM AND DISEASE PREVENTIONS
Project Number: 3092-51000-055-20
Specific Cooperative Agreement
Start Date: Apr 01, 2009
End Date: Mar 31, 2014
Objective 1: Establish a model using caesarean-delivered animal model to investigate the impact of prematurity on the gastrointestinal and metabolic response to perinatal nutrition.
Subobjective 1A: Quantify the effect of chronic parenteral nutrition in the first 2 weeks after birth on the short-term (3 months) and long-term (12 months) development of body composition and glucose homeostasis in models delivered preterm and at term.
Subobjective 1B: Quantify whether manipulation of dietary macronutrients and supplementation with bioactive food ingredients fed to premature animal models prevents the onset of mucosal inflammation and gastrointestinal disease, specifically necrotizing enterocolitis.
Objective 2: Compare the impact of continuous versus intermittent bolus delivery of nutrients provided enterally or parenterally on protein synthesis and accretion in neonatal animal models and identify the intracellular signaling mechanism involved.
Subobjective 2A: Compare the short-term effects of enteral or parenteral amino acids provided in a continuous vs. intermittent bolus delivery pattern.
Subobjective 2B: Compare the short-term effects of an enteral or parenteral complete diet provided in a continuous vs. intermittent bolus delivery pattern.
Subobjective 2C: Compare the long-term effects of an enteral or parenteral complete diet provided in a continuous vs. intermittent bolus delivery pattern.
The goal of our research is to determine how key nutrients, bioactive ingredients, and the pattern of nutrient delivery affects nutrient metabolism, body composition and incidence of disease in early postnatal life. Children's Nutrition Research Center researchers will use multiple experimental approaches involving innovative neonatal animal models to specifically examine the effects of prematurity, parenteral nutrition, and intermittent bolus feeding versus continuous feeding on glucose and protein metabolism. Main endpoints of metabolism will include measurements of glucose tolerance and insulin sensitivity using hyperinsulinemic, euglycemic clamps. The metabolic fate of amino acids and glucose will be measured using oxidation and incorporation of stable isotopic tracers into end-products such as CO2 and protein. Our research team will also examine whether specific carbohydrates and treatment with the bioactive gut peptide, glucagon-like peptide-2, can prevent the onset of necrotizing enterocolitis using a novel premature animal model. We will quantify endpoints of gastrointestinal function, such as blood flow and nutrient absorption, as well as disease based on measures of proinflammatory cytokine expression and gut microbiota communities. This research will provide novel information that will be directly useful to optimize the nutritional management of low birth weight infants and reduce the risk of early postnatal diseases.