PERINATAL STUDIES OF DISORDERS OF FETAL METABOLISM

Case Western Reserve University, Cleveland OH

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Abstract

The long range objective of the Perinatal Emphasis Research Center is to explore the influence of maternal metabolic environment and its perturbations on maternal, fetal and newborn metabolism and growth. Since fetal and neonatal growth, differentiation and organization can be affected both by environmental and genetic programming, additional goals of these studies are to identify the influences of these factors, metabolic of genetic, on key regulatory events in the newborn, and explore the mechanism(s) involved. The proposed hypotheses are based upon a large number of physiologically important data generated in the Center during the previous grant period. Six projects are presented. Molecular, genetic and stable isotope methods are employed in human and animal studies. The unique nature of the Center is the direct examination of biologically important questions in human studies. Projects 1 and 2 examine the genetic and environmental factors involved in the development of insulin resistance in human pregnancy and in animal models of gestational diabetes. Intracellular signaling pathway will be examined to explore the mechanism(s) involved. Project 3 uses stable isotope methods to examine the maternal nitrogen metabolism to describe the mechanism of nitrogen conservation and its regulation. Project 4 examines the role of maternal environmental factors, i.e. diet and physical activity, during pregnancy in human studies on prenatal growth and postnatal growth and development. Project 5 explores the molecular mechanism responsible for metabolic imprinting observed with early nutrient intervention in a neonatal rat model that results in a permanent hyperinsulinemia and obesity. Project 6 continues to examine a key event in extrauterine adaptation and survival, i.e. the regulation of glucose homeostasis and the role played by two transcription factors C/EBPalpha and C/EBPbeta in genetic patterning of glucose metabolism. All of the projects are scientifically interactive and utilize the core laboratories. These studies are likely to contribute to our understanding of metabolic influences on fetal and neonatal growth, on maternal metabolism and health, and may develop intervention strategies for disease states.