scholarly journals Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex

2016 ◽  
Vol 113 (29) ◽  
pp. 8182-8187 ◽  
Author(s):  
Jing Tian ◽  
Joseph L. Goldstein ◽  
Michael S. Brown
Keyword(s):  
Regulatory Element ◽  
Lipid Synthesis ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Gene Encoding ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Liver Nuclei ◽  
Factor C

Insulin increases lipid synthesis in liver by activating transcription of the gene encoding sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c activates the transcription of all genes necessary for fatty acid synthesis. Insulin induction of SREBP-1c requires LXRα, a nuclear receptor. Transcription of SREBP-1c also requires transcription factor C/EBPβ, but a connection between LXRα and C/EBPβ has not been made. Here we show that LXRα and C/EBPβ form a complex that can be immunoprecipitated from rat liver nuclei. Chromatin immunoprecipitation assays showed that the LXRα-C/EBPβ complex binds to the SREBP-1c promoter in a region that contains two binding sites for LXRα and is known to be required for insulin induction. Knockdown of C/EBPβ in fresh rat hepatocytes or mouse livers in vivo reduces the ability of insulin to increase SREBP-1c mRNA. The LXRα-C/EBPβ complex is bound to the SREBP-1c promoter in the absence or presence of insulin, indicating that insulin acts not by increasing the formation of this complex, but rather by activating it.

scholarly journals CRISPR/Cas9-mediated editing of Δ5 and Δ6 desaturases impairs Δ8-desaturation and docosahexaenoic acid synthesis in Atlantic salmon (Salmo salar L.)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alex K. Datsomor ◽  
Rolf E. Olsen ◽  
Nikola Zic ◽  
Angelico Madaro ◽  
Atle M. Bones ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Fatty Acyl ◽  
Chain Polyunsaturated Fatty Acid ◽  
Pufa Diet ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
High Degree

AbstractThe in vivo functions of Atlantic salmon fatty acyl desaturases (fads2), Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2 in long chain polyunsaturated fatty acid (LC-PUFA) synthesis in salmon and fish in general remains to be elucidated. Here, we investigate in vivo functions and in vivo functional redundancy of salmon fads2 using two CRISPR-mediated partial knockout salmon, Δ6abc/5Mt with mutations in Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2, and Δ6bcMt with mutations in Δ6fads2-b and Δ6fads2-c. F0 fish displaying high degree of gene editing (50–100%) were fed low LC-PUFA and high LC-PUFA diets, the former containing reduced levels of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids but higher content of linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acids, and the latter containing high levels of 20:5n-3 and 22:6n-3 but reduced compositions of 18:2n-6 and 18:3n-3. The Δ6abc/5Mt showed reduced 22:6n-3 levels and accumulated Δ6-desaturation substrates (18:2n-6, 18:3n-3) and Δ5-desaturation substrate (20:4n-3), demonstrating impaired 22:6n-3 synthesis compared to wildtypes (WT). Δ6bcMt showed no effect on Δ6-desaturation compared to WT, suggesting Δ6 Fads2-a as having the predominant Δ6-desaturation activity in salmon, at least in the tissues analyzed. Both Δ6abc/5Mt and Δ6bcMt demonstrated significant accumulation of Δ8-desaturation substrates (20:2n-6, 20:3n-3) when fed low LC-PUFA diet. Additionally, Δ6abc/5Mt demonstrated significant upregulation of the lipogenic transcription regulator, sterol regulatory element binding protein-1 (srebp-1) in liver and pyloric caeca under reduced dietary LC-PUFA. Our data suggest a combined effect of endogenous LC-PUFA synthesis and dietary LC-PUFA levels on srebp-1 expression which ultimately affects LC-PUFA synthesis in salmon. Our data also suggest Δ8-desaturation activities for salmon Δ6 Fads2 enzymes.

scholarly journals MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuhua Zhao ◽  
Lu Cheng ◽  
Yuan Shi ◽  
Jia Li ◽  
Qinghui Yun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Mtor Signaling Pathway ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Transcriptional Target

AbstractMIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has no significant effect on fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo fatty acid synthesis through up-regulating the expression of sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted cholesterol biosynthesis through up-regulating the expression of sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and metastasis assays indicated that MIEF2-regulated fatty acid synthesis and cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this malignancy.

scholarly journals Mutation in the Gene Encoding Sterol Regulatory Element Binding Protein (SREBP-2) in Hyper-Cholesterolaemic Subjects

2007 ◽  
Vol 7 (4) ◽  
pp. 315-317 ◽  
Author(s):  
Vivek Pratap Singh ◽  
Nakul Sinha ◽  
V. Ramesh ◽  
Satyendra Tewari ◽  
Faisal Khan ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Gene Encoding ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals A New Role for Sterol Regulatory Element Binding Protein 1 Transcription Factors in the Regulation of Muscle Mass and Muscle Cell Differentiation

2009 ◽  
Vol 30 (5) ◽  
pp. 1182-1198 ◽  
Author(s):  
Virginie Lecomte ◽  
Emmanuelle Meugnier ◽  
Vanessa Euthine ◽  
Christine Durand ◽  
Damien Freyssenet ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Muscle Mass ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Myogenic Program

ABSTRACT The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.

Structure of the Human Gene Encoding Sterol Regulatory Element Binding Protein 2 (SREBF2)

Genomics ◽  
1997 ◽  
Vol 40 (1) ◽  
pp. 31-40 ◽  
Author(s):  
André R. Miserez ◽  
Guoqing Cao ◽  
Lori C. Probst ◽  
Helen H. Hobbs
Keyword(s):  
Human Gene ◽  
Binding Protein ◽  
Regulatory Element ◽  
Gene Encoding ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo

2010 ◽  
Vol 107 (40) ◽  
pp. 17321-17326 ◽  
Author(s):  
T. Horie ◽  
K. Ono ◽  
M. Horiguchi ◽  
H. Nishi ◽  
T. Nakamura ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element
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