Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver

Biochimie ◽  
2005 ◽  
Vol 87 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Renaud Dentin ◽  
Jean Girard ◽  
Catherine Postic
Keyword(s):  
Glucose Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Responsive Element

scholarly journals Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumor growth

2013 ◽  
Vol 1 (1) ◽  
pp. 3 ◽  
Author(s):  
Beatrice Griffiths ◽  
Caroline A Lewis ◽  
Karim Bensaad ◽  
Susana Ros ◽  
Qifeng Zhang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Survival ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Sterol Regulatory Element Binding Protein Regulates the Expression and Metabolic Functions of Wild-Type and OncogenicIDH1

2016 ◽  
Vol 36 (18) ◽  
pp. 2384-2395 ◽  
Author(s):  
Stéphane J. H. Ricoult ◽  
Christian C. Dibble ◽  
John M. Asara ◽  
Brendan D. Manning
Keyword(s):  
Carbon Flux ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Reducing Power ◽  
Isocitrate Dehydrogenase 1 ◽  
Metabolic Functions ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Sterol regulatory element binding protein (SREBP) is a major transcriptional regulator of the enzymes underlyingde novolipid synthesis. However, little is known about the SREBP-mediated control of processes that indirectly support lipogenesis, for instance, by supplying reducing power in the form of NAPDH or directing carbon flux into lipid precursors. Here, we characterize isocitrate dehydrogenase 1 (IDH1) as a transcriptional target of SREBP across a spectrum of cancer cell lines and human cancers. IDH1 promotes the synthesis of lipids specifically from glutamine-derived carbons. Neomorphic mutations in IDH1 occur frequently in certain cancers, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG). We found that SREBP induces the expression of oncogenic IDH1 and influences 2-HG production from glucose. Treatment of cells with 25-hydroxycholesterol or statins, which respectively inhibit or activate SREBP, further supports SREBP-mediated regulation of IDH1 and, in cells with oncogenic IDH1, carbon flux into 2-HG.

scholarly journals Sterol Regulatory Element Binding Protein 2 Overexpression Is Associated With Reduced Adipogenesis and Ectopic Fat Accumulation in Transgenic Spontaneously Hypertensive Rats

2014 ◽  
pp. 587-590 ◽  
Author(s):  
V. LANDA ◽  
V. ZÍDEK ◽  
P. MLEJNEK ◽  
M. ŠIMÁKOVÁ ◽  
J. ŠILHAVÝ ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Relative Weight ◽  
Ectopic Fat ◽  
Transgenic Rats ◽  
Fat Accumulation ◽  
Spontaneously Hypertensive ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

It has been reported that the major function of the sterol regulatory element binding protein 2 (SREBP-2) is to activate preferentially cholesterol biosynthesis in liver and adipose tissue rather than fatty acid synthesis. In the current study, we analyzed the effects of overexpression of human dominant-positive SREBP-2 transgene under control of PEPCK promoter in the spontaneously hypertensive rat (SHR) on lipid and glucose metabolism. Transgenic overexpression of SREBP-2 was associated with significantly higher hepatic triglycerides (20.4±0.9 vs. 17.0±0.05 µmol/g, P<0.05) but not cholesterol (10.6±0.4 vs. 10.9±0.4 µmol/g) and decreased relative weight of epididymal fat pad (0.73±0.03 vs. 0.830.03, P<0.05). In addition, muscle triglyceride (15.8±3.7 vs. 8.5±1.2 µmol/g, P<0.001) and cholesterol (3.6±0.5 vs. 2.1±0.1 µmol/g, P<0.05) concentrations were significantly increased in transgenic rats when compared to SHR controls. Ectopic fat accumulation was associated with significantly increased serum glucose levels (6.4±0.1 vs. 5.9±0.1 mmol/l, P<0.005) and reduced insulin levels (1.78±0.33 vs. 2.73±0.37 nmol/l, P<0.05) in transgenic rats. These results provide evidence for important role of SREBP-2 in regulation of lipid and glucose metabolism.

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