Many epidemiological studies have shown a correlation between intrauterine growth retardation and the onset of insulin resistance, NIDDM, hypertension, hyperlipidemia and cardiovascular diseases. This association has been explained by a concept termed re-programming, whereby intrauterine exposure to insufficient nutrient supply during critical periods of fetal life would permanently affect the development and function of the endocrine system, leading to metabolic changes, including insulin resistance. Knowledge of the mechanisms of re-programming might allow new strategies for early prevention of long-term metabolic disturbances like diabetes. This project will examine the relationship between intrauterine growth retardation (IUGR), insulin resistance and fetal growth, using fetal hepatic growth in rats as a model. This study will serve to characterize the mechanisms involved in the signal transdution pathways and the cell cycle that promote growth in the liver of IUGR rats, thereby demonstrating the effects of maternal fasting on hepatic growth. With this knowledge, the concept of re-programming may be better understood to help explain fetal origins of adult disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HD041893-03
Application #
6702204
Study Section
Special Emphasis Panel (ZRG1-REN (20))
Program Officer
Grave, Gilman D
Project Start
2002-08-15
Project End
Budget Start
2004-02-15
Budget End
2005-02-14
Support Year
3
Fiscal Year
2004
Total Cost
$44,514
Indirect Cost
Name
Brown University
Department
Pathology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Jimenez, Rosa H; Lee, Ju-Seog; Francesconi, Mirko et al. (2010) Regulation of gene expression in hepatic cells by the mammalian Target of Rapamycin (mTOR). PLoS One 5:e9084
Yoo, Sunny J-S; Jimenez, Rosa H; Sanders, Jennifer A et al. (2008) The alpha4-containing form of protein phosphatase 2A in liver and hepatic cells. J Cell Biochem 105:290-300