Regulation of intestinal fructose transport in neonatal rats

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This study will examine how intestinal nutrient transport systems adapt to marked changes in nutrient types and concentrations occurring at birth and at weaning. At birth, the small intestine abruptly acquires a new function: to absorb nutrients from milk. During weaning, the intestine has to manufacture different types or different numbers of transporters. How do intestinal cells make, and 'know' when to make, these transporters? The long-term objective of this project is to determine the mechanisms regulating intestinal nutrient transport during development. The intestinal fructose transporter GLUT5 is normally not made until after completion of weaning. However, precocious introduction of its substrate, dietary fructose, dramatically induces the early appearance of this transporter. This project will determine the genes that change their expression when fructose stimulates GLUT5 during weaning. It will then identify which of these factors mediate the effect of dietary fructose by using cell-permeable, pharmacological agents that stimulate or inhibit their action. If these agents alter the effect of fructose on GLUT5, then their target proteins likely play important roles in transducing the dietary signal to the GLUT5 gene. The location of these factors in the intestine will be determined by dye-containing probes that specifically recognize them. Thus, the results of this study will provide important new information to understand the regulation of nutrient transporters during development. In addition, by examining nutrient-responsive regulatory mechanisms controlling gut development, this project can determine the potential of reprogramming normal developmental patterns of absorption in order to allow the intestine to process nutrients at an earlier stage of development. This knowledge would increase our understanding of mechanisms that control intestinal growth and maturation in premature infants. Fructose is a very common ingredient in American diets, and these studies have major nutritional significance. Further, this project will also support the training and education of postdoctoral fellows and students.