COBRE Pilot: Endogenous Ligand for NR4A1 Orphan Nuclear Receptor and Systemic Metabolism

Title: Endogenous ligand for NR4A1 orphan nuclear receptor and systemic metabolism ABSTRACT: NR4A1 is an orphan nuclear receptor regulating metabolism at cellular and systemic levels. NR4A1 is regarded as a potential therapeutic target for metabolic diseases and cancer. Although NR4A1 is regulated by metabolic conditions, the mechanism connecting metabolic conditions and NR4A1 function is not well understood. In this project, I hypothesize that glucose-1-phosphate (G1P) regulates NR4A1 in response to metabolic conditions and that this interaction can be used to lower blood glucose level in vivo. This hypothesis is supported by preliminary in vitro and cellular data. In this project, I will test this hypothesis by experiments using cells and mice. Outcomes of this project will address a critical barrier in the field by identifying a mechanism regulating NR4A1 in response to metabolic stimuli and by providing a reagent to regulate carbohydrate/fatty acid metabolism in vivo. This project is relevant to COCVD’s missions, which include identification of mechanisms linking obesity to diseases as a mechanism connecting metabolic conditions, gene expression, and metabolic disorders is investigated.