Activated Sterol Regulatory Element-Binding Protein-2 Suppresses Hepatocyte Nuclear Factor-4-Mediated Cyp3a11 Expression in Mouse Liver

2010 ◽  
Vol 79 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Shin-ichi Inoue ◽  
Kouichi Yoshinari ◽  
Mika Sugawara ◽  
Yasushi Yamazoe
Keyword(s):  
Mouse Liver ◽  
Binding Protein ◽  
Regulatory Element ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Hepatocyte Nuclear Factor 4

Analysis of Sterol-Regulatory Element-Binding Protein 1c Target Genes in Mouse Liver during Aging and High-Fat Diet

2013 ◽  
Vol 6 (2) ◽  
pp. 107-122 ◽  
Author(s):  
Frédéric Capel ◽  
Gaëlle Rolland-Valognes ◽  
Catherine Dacquet ◽  
Manuel Brun ◽  
Michel Lonchampt ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Mouse Liver ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
High Fat ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Inhibition of cannabinoid CB1 receptor upregulates Slc2a4 expression via nuclear factor-κB and sterol regulatory element-binding protein-1 in adipocytes

2012 ◽  
Vol 49 (2) ◽  
pp. 97-106 ◽  
Author(s):  
D T Furuya ◽  
A C Poletto ◽  
H S Freitas ◽  
U F Machado
Keyword(s):  
Glucose Transporter ◽  
Binding Protein ◽  
Regulatory Element ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Mobility Shift ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Evidences have suggested that the endocannabinoid system is overactive in obesity, resulting in enhanced endocannabinoid levels in both circulation and visceral adipose tissue. The blockade of cannabinoid receptor type 1 (CB1) has been proposed for the treatment of obesity. Besides loss of body weight, CB1 antagonism improves insulin sensitivity, in which the glucose transporter type 4 (GLUT4) plays a key role. The aim of this study was to investigate the modulation of GLUT4-encoded gene (Slc2a4 gene) expression by CB1 receptor. For this, 3T3-L1 adipocytes were incubated in the presence of a highly selective CB1 receptor agonist (1 μM arachidonyl-2′-chloroethylamide) and/or a CB1 receptor antagonist/inverse agonist (0.1, 0.5, or 1 μM AM251, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide). After acute (2 and 4 h) and chronic (24 h) treatments, cells were harvested to evaluate: i) Slc2a4, Cnr1 (CB1 receptor-encoded gene), and Srebf1 type a (SREBP-1a type-encoded gene) mRNAs (real-time PCR); ii) GLUT4 protein (western blotting); and iii) binding activity of nuclear factor (NF)-κB and sterol regulatory element-binding protein (SREBP)-1 specifically in the promoter of Slc2a4 gene (electrophoretic mobility shift assay). Results revealed that both acute and chronic CB1 receptor antagonism greatly increased (∼2.5-fold) Slc2a4 mRNA and protein content. Additionally, CB1-induced upregulation of Slc2a4 was accompanied by decreased binding activity of NF-κB at 2 and 24 h, and by increased binding activity of the SREBP-1 at 24 h. In conclusion, these findings reveal that the blockade of CB1 receptor markedly increases Slc2a4/GLUT4 expression in adipocytes, a feature that involves NF-κB and SREBP-1 transcriptional regulation.

scholarly journals Functional Interaction of Hepatic Nuclear Factor-4 and Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α in CYP7A1 Regulation Is Inhibited by a Key Lipogenic Activator, Sterol Regulatory Element-Binding Protein-1c

2007 ◽  
Vol 21 (11) ◽  
pp. 2698-2712 ◽  
Author(s):  
Bhaskar Ponugoti ◽  
Sungsoon Fang ◽  
Jongsook Kim Kemper
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Dominant Negative Mutant ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Functional Interaction ◽  
Peroxisome Proliferator Activated Receptor ◽  
Histone Deacetylase 2 ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Abstract Insulin inhibits transcription of cholesterol 7α-hydroxylase (Cyp7a1), a key gene in bile acid synthesis, and the hepatic nuclear factor-4 (HNF-4) site in the promoter was identified as a negative insulin response sequence. Using a fasting/feeding protocol in mice and insulin treatment in HepG2 cells, we explored the inhibition mechanisms. Expression of sterol regulatory element-binding protein-1c (SREBP-1c), an insulin-induced lipogenic factor, inversely correlated with Cyp7a1 expression in mouse liver. Interaction of HNF-4 with its coactivator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), was observed in livers of fasted mice and was reduced after feeding. Conversely, HNF-4 interaction with SREBP-1c was increased after feeding. In vitro studies suggested that SREBP-1c competed with PGC-1α for direct interaction with the AF2 domain of HNF-4. Reporter assays showed that SREBP-1c, but not of a SREBP-1c mutant lacking the HNF-4 interacting domain, inhibited HNF-4/PGC-1α transactivation of Cyp7a1. SREBP-1c also inhibited PGC-1α-coactivation of estrogen receptor, constitutive androstane receptor, pregnane X receptor, and farnesoid X receptor, implying inhibition of HNF-4 by SREBP-1c could extend to other nuclear receptors. In chromatin immunoprecipitation studies, HNF-4 binding to the promoter was not altered, but PGC-1α was dissociated, SREBP-1c and histone deacetylase-2 (HDAC2) were recruited, and acetylation of histone H3 was decreased upon feeding. Adenovirus-mediated expression of a SREBP-1c dominant-negative mutant, which blocks the interaction of SREBP-1c and HNF-4, partially but significantly reversed the inhibition of Cyp7a1 after feeding. Our data show that SREBP-1c functions as a non-DNA-binding inhibitor and mediates, in part, suppression of Cyp7a1 by blocking functional interaction of HNF-4 and PGC-1α. This mechanism may be relevant to known repression of many other HNF-4 target genes upon feeding.

scholarly journals Sterol Regulatory Element-binding Protein-1 (SREBP-1) Is Required to Regulate Glycogen Synthesis and Gluconeogenic Gene Expression in Mouse Liver

2014 ◽  
Vol 289 (9) ◽  
pp. 5510-5517 ◽  
Author(s):  
Rafaela Ruiz ◽  
Victoria Jideonwo ◽  
Miwon Ahn ◽  
Sneha Surendran ◽  
Vincent S. Tagliabracci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Binding Protein ◽  
Regulatory Element ◽  
Glycogen Synthesis ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Increased Expression of the Sterol Regulatory Element-binding Protein-1 Gene in Insulin Receptor Substrate-2−/−Mouse Liver

2001 ◽  
Vol 276 (42) ◽  
pp. 38337-38340 ◽  
Author(s):  
Kazuyuki Tobe ◽  
Ryo Suzuki ◽  
Masashi Aoyama ◽  
Toshimasa Yamauchi ◽  
Junji Kamon ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Mouse Liver ◽  
Binding Protein ◽  
Regulatory Element ◽  
Insulin Receptor Substrate ◽  
Element Binding Protein ◽  
Sterol Regulatory Element
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