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HARVARD COLLEGE, PRESIDENT & FELLOWS OF

The scope of the award is to examine the function of the nuclear receptor peroxisome proliferator-activated receptor delta in the liver and to test the hypothesis that this receptor regulates hepatic gene programs that promote glucose utilization for the synthesis of glycogen and fatty acids. For loss-of-function studies, we have proposed to generate liver-specific peroxisome proliferator-activated receptor delta-/- mice by crossing peroxisome proliferator-activated receptor f/f allele to albumin-cre transgene (liver-specific peroxisome proliferator-activated receptor knockout ). We have now generated cohorts of liver-specific peroxisome proliferator-activated receptor knockout mice and are at the stage of making significant progress. Funds are requested to purchase a real-time PCR machine and to support the salary of a research assistant to facilitate research using this mouse model to identify molecular targets of peroxisome proliferator-activated receptor delta in the liver. This will be achieved in two aims: aim 1 will determine transcriptional programs regulated by peroxisome proliferator-activated receptor delta at the fed and fasted state and aim 2 will determine transcriptional programs regulated by peroxisome proliferator-activated receptor delta on a chow or high fat diet. These studies are a key component of the proposal, as identification of transcriptional programs controlled by peroxisome proliferator-activated receptor delta may provide a molecular basis for developing drugs to control glucose and lipid homeostasis.

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