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
Biology
Lipid metabolism
NR4A nuclear receptors
NR4A1
Nur77
SREBP1c
Sterol regulatory element binding protein-1
ABC transporter
ABC transporter G5
ABC transporter G8
acyl coenzyme A desaturase
acyl coenzyme A desaturase 1
adenovirus vector
fatty acid synthase
glycerol 3 phosphate acyltransferase
low density lipoprotein receptor
nuclear receptor Nur77
sterol regulatory element binding protein 1c
triacylglycerol
animal experiment
animal tissue
article
controlled study
enzyme activity
enzyme repression
gene expression
genetic analysis
lipid blood level
lipid liver level
lipid metabolism
male
mouse
nonhuman
nucleotide sequence
priority journal
protein expression
protein function
Adenoviridae
Animals
DNA-Binding Proteins
Gene Expression Regulation
Lipid Metabolism
Liver
Male
Mice
Mice, Inbred C57BL
Receptors, Cytoplasmic and Nuclear
Receptors, Steroid
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
Transcription Factors
Triglycerides
Mus
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