Metabolic regulation by the nuclear receptor corepressor RIP140.
Whereas the importance of activating gene expression in metabolic pathways to control energy homeostasis is well established, the contribution of transcriptional inhibition is less well defined. In this review we highlight a crucial role of RIP140, a transcriptional corepressor for nuclear receptors, in the regulation of energy expenditure. Mice devoid of the RIP140 gene are lean, exhibit resistance to high-fat-diet-induced obesity, and have increased glucose tolerance and insulin sensitivity. Consistent with these observations, RIP140 suppresses the expression of gene clusters that are involved in lipid and carbohydrate metabolism, including fatty acid oxidation, oxidative phosphorylation and mitochondrial uncoupling. Therefore, the functional interplay between transcriptional activators and the corepressor RIP140 is an essential process in metabolic regulation.
Christian
Mark
M
Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, Du Cane Road, London W12 0NN, UK.
White
Roger
R
Parker
Malcolm G
MG
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D050218:Body Fat Distribution; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D000078723:Nuclear Receptor Interacting Protein 1; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C539127:NCOR1 protein, human; C000627127:NRIP1 protein, human; C539128:Ncor1 protein, mouse; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D000078723:Nuclear Receptor Interacting Protein 1; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins