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The Nuclear Receptor Cofactor, Receptor-Interacting Protein 140, Is Required for the Regulation of Hepatic Lipid and Glucose Metabolism by Liver X Receptor

Institute of Reproductive and Developmental Biology (B.H., M.H., A.S., R.W., M.G.P.), and Medical Research Council Cellular Stress Group, Clinical Sciences Centre (A.W.), Imperial College London, Faculty of Medicine, London W12 0NN, United Kingdom

Address all correspondence and requests for reprints to: Malcolm G. Parker, Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom. E-mail: m.parker{at}imperial.ac.uk.

The liver X receptors (LXRs) are nuclear receptors that play important roles in the regulation of lipid metabolism. In this study, we demonstrate that receptor-interacting protein 140 (RIP140) is a cofactor for LXR in liver. Analysis of RIP140 null mice and hepatocytes depleted of RIP140 indicate that the cofactor is essential for the ability of LXR to activate the expression of a set of genes required for lipogenesis. Furthermore we demonstrate that RIP140 is required for the ability of LXR to repress the expression of the phosphoenolpyruvate carboxykinase gene in Fao cells and mice. Thus, we conclude that the function of RIP140 as a cofactor for LXR in liver varies according to the target genes and metabolic process, serving as a coactivator in lipogenesis but as a corepressor in gluconeogenesis.

NURSA Molecule Pages Link:

Nuclear Receptors:   LXRβ  |  LXRα

Coregulators:   RIP140

Ligands:   T0901317

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