Print Email Facebook Twitter Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity Title Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity Author Pols, T.W.H. Ottenhoff, R. Vos, M. Levels, J.H.M. Quax, P.H.A. Meijers, J.C.M. Pannekoek, H. Groen, A.K. de Vries, C.J.M. TNO Kwaliteit van Leven Publication year 2008 Abstract NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity. © 2007 Elsevier Inc. All rights reserved. Chemicals / CAS: acyl coenzyme A desaturase, 9014-34-0; fatty acid synthase, 9045-77-6; glycerol 3 phosphate acyltransferase, 9029-96-3; DNA-Binding Proteins; orphan nuclear receptor NGFI-B, 121479-42-3; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Triglycerides Subject BiologyLipid metabolismNR4A nuclear receptorsNR4A1Nur77SREBP1cSterol regulatory element binding protein-1ABC transporterABC transporter G5ABC transporter G8acyl coenzyme A desaturaseacyl coenzyme A desaturase 1adenovirus vectorfatty acid synthaseglycerol 3 phosphate acyltransferaselow density lipoprotein receptornuclear receptor Nur77sterol regulatory element binding protein 1ctriacylglycerolanimal experimentanimal tissuearticlecontrolled studyenzyme activityenzyme repressiongene expressiongenetic analysislipid blood levellipid liver levellipid metabolismmalemousenonhumannucleotide sequencepriority journalprotein expressionprotein functionAdenoviridaeAnimalsDNA-Binding ProteinsGene Expression RegulationLipid MetabolismLiverMaleMiceMice, Inbred C57BLReceptors, Cytoplasmic and NuclearReceptors, SteroidRNA, MessengerSterol Regulatory Element Binding Protein 1Transcription FactorsTriglyceridesMus To reference this document use: http://resolver.tudelft.nl/uuid:cbfa08d7-a5ff-408f-b826-3689c836da4a DOI https://doi.org/10.1016/j.bbrc.2007.12.039 TNO identifier 240659 ISSN 0006-291X Source Biochemical and Biophysical Research Communications, 366 (4), 910-916 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.