Retinoids regulate gene expression at the level of transcription by activating nuclear receptors and thereby triggering specific signalling cascades. The RXR family of receptors heterodimerize with other nuclear receptors to regulate gene expression. The role for these master regulators is not clearly understood. The proposed studies will take advantage of the fact that an RXR-specific ligand can produce an acute effect in 3T3-L1 differentiated adipocytes. We will examine the molecular basis by which this ligand dramatically decreases lipoprotein lipase (LPL) activity and specifically address the hypothesis that the action of the RXR ligand depends on activation of the RXR/PPAR heterodimeric complex in 3T3-L1 adipocytes and that this activated complex acutely alters the transcription of genes that control LPL activity. To test this hypothesis, we will first determine the relation between the RXR signalling pathway to that of the PPAR signalling pathway. Secondly, we will identify novel genes that acutely respond to the RXR ligand and control LPL activity. These data will provide information regarding the role of the RXR pathway in intracellular metabolism and the basis for future research to characterize the mechanism of this pathway in disorders involving adipocyte homeostasis.
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| Depre, C; Young, M E; Ying, J et al. (2000) Streptozotocin-induced changes in cardiac gene expression in the absence of severe contractile dysfunction. J Mol Cell Cardiol 32:985-96 |
