Orphan nuclear receptor TR4 and fibroblast growth factor 1 in metabolism

Metabolic homeostasis is achieved, in part, through the coordinated activities of members of the Nuclear Receptor (NR) family, a superfamily of ligand-modulated transcription factors (TFs) that mediate responses to a wide range of lipophilic signaling molecules including lipids, steroids, retinoids, hormones and xenobiotics. As sensors for these signals, they provide an important link between the environment and the organism’s physiological response. Their general ability to bind ligands makes this family an ideal therapeutic target. Indeed, 13% of FDA approved therapeutics on the market today target the NR-family, including drugs for the treatment of insulin resistance (glitazones, TZDs), hyperlipidemia (fibrates), inflammation (dexamethasone) and cancer (tamoxifen) . Thus, NRs have become a primary target for drug development aimed at metabolic disease.
In this thesis we set out to investigate the roles of orphan nuclear receptor TR4 in the development of metabolic diseases and of fibroblast growth factor 1 (FGF1), a recently identified target of nuclear receptor PPARγ, in the development of non-alcoholic liver disease .