Project Number: 6250-51000-044-00
Start Date: May 21, 2004
End Date: Mar 30, 2009
1. Identify nutritional products and other natural products that regulate the activity of nuclear hormone receptors, with a specific focus on PPAR (Peroxisome Proliferator Activated Receptor) isoforms, define the active agents that modulate receptor functions, and characterize the actions of such agents at the levels of receptor function and target genes. 2. There is a 6-fold increase in the soluble maltase-glucoamylase message in mice with membrane maltase-glucoamylase ablation. This increase is present in suckling as well as weaned null mice. This presents a novel model of gene regulation by dietary carbohydrates. The regulatory genes involved in this upregulation are under investigation by microarray analysis and will be confirmed and extended by mechanistic in vitro studies in the mICcl2 cell line. 3. Measure the effects of specific PPAR(alpha) and PPAR(beta/delta) agonists on metabolic gene expression in isolated cardiomyocytes; and by determining whether loss of PPAR(alpha) and PPAR(beta/delta) attenuates the effects of distinct fatty acid species on metabolic gene expression in the mouse model. 4. Investigate the genetic background on endogenous supply of ornithine and the presentation of urea cycles disorders.