scholarly journals Effects of fish oil and conjugated linoleic acids on expression of target genes of PPARα and sterol regulatory element-binding proteins in the liver of laying hens

2008 ◽  
Vol 100 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Bettina König ◽  
Julia Spielmann ◽  
Kati Haase ◽  
Corinna Brandsch ◽  
Holger Kluge ◽  
...  
Keyword(s):  
Fish Oil ◽  
Binding Proteins ◽  
Target Genes ◽  
Laying Hens ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Control Fish ◽  
Mrna Levels ◽  
Conjugated Linoleic Acids ◽  
Sterol Regulatory Element

In mammals, (n-3) PUFA and conjugated linoleic acids (CLA) act as activators of PPARα and alter nuclear concentrations of sterol regulatory element-binding proteins (SREBP) in the liver, and thereby influence hepatic lipid catabolism and synthesis. In this study, we investigated the hypothesis that (n-3) PUFA and CLA exert similar effects in the liver of laying hens. Thirty hens (64 weeks old) were fed diets containing 30 g/kg of sunflower oil (control), fish oil (salmon oil) or CLA in TAG form (containing predominantlycis-9,trans-11 CLA andtrans-10,cis-12 CLA) for 5 weeks. Hens fed fish oil had a higher expression of some PPARα target genes and a lower nuclear concentration of SREBP-2 in the liver and lower concentrations of cholesterol and TAG in plasma than control hens. Nuclear concentration of SREBP-1 and its target genes involved in lipogenesis were not altered in hens fed fish oil. Hens fed CLA had increased concentrations of TAG and cholesterol in the liver. However, their mRNA levels of PPARα target genes and nuclear concentrations of SREBP-1 and SREBP-2 as well as mRNA levels of their target genes in the liver were largely unchanged compared to control hens. The results of this study suggest that (n-3) PUFA cause a moderate activation of PPARα and lower cholesterol synthesis but do not impair fatty acid synthesis in the liver of laying hens. CLA lead to an accumulation of TAG and cholesterol in the liver of hens by mechanisms to be elucidated in further studies.

PO7-181 DESMOSTEROL CAN REGULATE THE PROCESSING OF THE STEROL REGULATORY ELEMENT BINDING PROTEINS AND THE EXPRESSION OF TARGET GENES

2007 ◽  
Vol 8 (1) ◽  
pp. 62
Author(s):  
S. Rodriguez-Acebes ◽  
J. Martinez-Botas ◽  
A. Davalos ◽  
M.A. Lasuncion ◽  
R.B. Rawson ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Target Genes ◽  
Regulatory Element ◽  
Sterol Regulatory Element

Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver

2004 ◽  
Vol 287 (6) ◽  
pp. E1039-E1048 ◽  
Author(s):  
Caroline Améen ◽  
Daniel Lindén ◽  
Britt-Mari Larsson ◽  
Agneta Mode ◽  
Agneta Holmäng ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Continuous Infusion ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Female Rats ◽  
Mrna Levels ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Secretory Pattern

We investigated whether the sexually dimorphic secretory pattern of growth hormone (GH) in the rat regulates hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes. SREBP-1c, fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT) mRNA were more abundant in female than in male livers, whereas acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) were similarly expressed in both sexes. Hypophysectomized female rats were given GH as a continuous infusion or as two daily injections for 7 days to mimic the female- and male-specific GH secretory patterns, respectively. The female pattern of GH administration increased the expression of SREBP-1c, ACC1, FAS, SCD-1, and GPAT mRNA, whereas the male pattern of GH administration increased only SCD-1 mRNA. FAS and SCD-1 protein levels were regulated in a similar manner by GH. Incubation of primary rat hepatocytes with GH increased SCD-1 mRNA levels and decreased FAS and GPAT mRNA levels but had no effect on SREBP-1c mRNA. GH decreased hepatic liver X receptor-α (LXRα) mRNA levels both in vivo and in vitro. Feminization of the GH plasma pattern in male rats by administration of GH as a continuous infusion decreased insulin sensitivity and increased expression of FAS and GPAT mRNA but had no effect on SREBP-1c, ACC1, SCD-1, or LXRα mRNA. In conclusion, FAS and GPAT are specifically upregulated by the female secretory pattern of GH. This regulation is not a direct effect of GH on hepatocytes and does not involve changed expression of SREBP-1c or LXRα mRNA but is associated with decreased insulin sensitivity.

scholarly journals Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium

2010 ◽  
Vol 299 (6) ◽  
pp. E918-E927 ◽  
Author(s):  
Michael C. Rudolph ◽  
Jenifer Monks ◽  
Valerie Burns ◽  
Meridee Phistry ◽  
Russell Marians ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Sterol Regulatory Element

The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase ( Fasn), insulin-induced gene 1 ( Insig1), mitochondrial citrate transporter ( Slc25a1), and stearoyl-CoA desaturase 2 ( Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α ( Acaca) and ATP citrate lyase ( Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.

New insights into the activation of sterol regulatory element-binding proteins by proteolytic processing

2013 ◽  
Vol 4 (4) ◽  
pp. 417-423 ◽  
Author(s):  
Jun Inoue ◽  
Ryuichiro Sato
Keyword(s):  
Endoplasmic Reticulum ◽  
Small Molecules ◽  
Recent Progress ◽  
Binding Proteins ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Proteolytic Processing ◽  
Endoplasmic Reticulum Membrane ◽  
Post Translational Modification ◽  
Sterol Regulatory Element

AbstractSterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate a wide variety of genes involved in cholesterol and fatty acid synthesis. After transcription, SREBPs are controlled at multiple post-transcriptional levels, including proteolytic processing and post-translational modification. Among these, proteolytic processing is a crucial regulatory step that activates SREBPs, which are synthesized as inactive endoplasmic reticulum membrane proteins. In this review, we focus on recent progress with regard to signaling pathways and small molecules that affect activation of SREBPs by proteolytic processing.

scholarly journals Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes

FEBS Journal ◽  
2011 ◽  
Vol 278 (15) ◽  
pp. 2739-2750 ◽  
Author(s):  
Jun Inoue ◽  
Yuka Ito ◽  
Satoko Shimada ◽  
Shin-ich Satoh ◽  
Takashi Sasaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Target Genes ◽  
Regulatory Element ◽  
Sterol Regulatory Element

scholarly journals Sterol Regulatory Element-Binding Proteins Are Regulators of the NIS Gene in Thyroid Cells

2013 ◽  
Vol 27 (5) ◽  
pp. 781-800 ◽  
Author(s):  
Robert Ringseis ◽  
Christine Rauer ◽  
Susanne Rothe ◽  
Denise K. Gessner ◽  
Lisa-Marie Schütz ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Target Genes ◽  
Regulatory Element ◽  
Strong Dependence ◽  
Transcriptional Regulators ◽  
Lipid Biosynthesis ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Nis Gene ◽  
Sterol Regulatory Element

Abstract The uptake of iodide into the thyroid, an essential step in thyroid hormone synthesis, is an active process mediated by the sodium-iodide symporter (NIS). Despite its strong dependence on TSH, the master regulator of the thyroid, the NIS gene was also reported to be regulated by non-TSH signaling pathways. In the present study we provide evidence that the rat NIS gene is subject to regulation by sterol regulatory element-binding proteins (SREBPs), which were initially identified as master transcriptional regulators of lipid biosynthesis and uptake. Studies in FRTL-5 thyrocytes revealed that TSH stimulates expression and maturation of SREBPs and expression of classical SREBP target genes involved in lipid biosynthesis and uptake. Almost identical effects were observed when the cAMP agonist forskolin was used instead of TSH. In TSH receptor-deficient mice, in which TSH/cAMP-dependent gene regulation is blocked, the expression of SREBP isoforms in the thyroid was markedly reduced when compared with wild-type mice. Sterol-mediated inhibition of SREBP maturation and/or RNA interference-mediated knockdown of SREBPs reduced expression of NIS and NIS-specific iodide uptake in FRTL-5 cells. Conversely, overexpression of active SREBPs caused a strong activation of the 5′-flanking region of the rat NIS gene mediated by binding to a functional SREBP binding site located in the 5′-untranslated region of the rat NIS gene. These findings show that TSH acts as a regulator of SREBP expression and maturation in thyroid epithelial cells and that SREBPs are novel transcriptional regulators of NIS.

scholarly journals Oleanolic Acid Diminishes Liquid Fructose-Induced Fatty Liver in Rats: Role of Modulation of Hepatic Sterol Regulatory Element-Binding Protein-1c-Mediated Expression of Genes Responsible for De Novo Fatty Acid Synthesis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Changjin Liu ◽  
Ying Li ◽  
Guowei Zuo ◽  
Wenchun Xu ◽  
Huanqing Gao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Target Genes ◽  
Nuclear Protein ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Oleanolic acid (OA), contained in more than 1620 plants and as an aglycone precursor for naturally occurred and synthesized triterpenoid saponins, is used in China for liver disorders in humans. However, the underlying liver-protecting mechanisms remain largely unknown. Here, we found that treatment of rats with OA (25 mg/kg/day, gavage, once daily) over 10 weeks diminished liquid fructose-induced excess hepatic triglyceride accumulation without effect on total energy intake. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in OA-treated rats. Hepatic gene expression profile demonstrated that OA suppressed fructose-stimulated overexpression of sterol regulatory element-binding protein-(SREBP-) 1/1c mRNA and nuclear protein. In accord, overexpression of SREBP-1c-responsive genes responsible for fatty acid synthesis was also downregulated. In contrast, overexpressed nuclear protein of carbohydrate response element-binding protein and its target genes liver pyruvate kinase and microsomal triglyceride transfer protein were not altered. Additionally, OA did not affect expression of peroxisome proliferator-activated receptor-gamma- and -alpha and their target genes. It is concluded that modulation of hepatic SREBP-1c-mediated expression of the genes responsible for de novo fatty acid synthesis plays a pivotal role in OA-elicited diminishment of fructose-induced fatty liver in rats.

scholarly journals Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms

2003 ◽  
Vol 372 (3) ◽  
pp. 811-819 ◽  
Author(s):  
Neale D. RIDGWAY ◽  
Thomas A. LAGACE
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Transcriptional Activation ◽  
Binding Proteins ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Transcriptional Level ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Sterol Regulatory Element

The synthesis of phosphatidylcholine (PtdCho) by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). Sterol regulatory element binding proteins (SREBPs) have been proposed to regulate CCT at the transcriptional level, or via the synthesis of lipid activators or substrates of the CDP-choline pathway. To assess the contributions of these two mechanisms, we examined CCTα expression and PtdCho synthesis by the CDP-choline pathway in cholesterol and fatty acid auxotrophic CHO M19 cells inducibly expressing constitutively active nuclear forms of SREBP1a or SREBP2. Induction of either SREBP resulted in increased expression of mRNAs for sterol-regulated genes, elevated fatty acid and cholesterol synthesis (>10–50-fold) and increased PtdCho synthesis (2-fold). CCTα mRNA was increased 2-fold by enforced expression of SREBP1a or SREBP2. The resultant increase in CCTα protein and activity (2-fold) was restricted primarily to the soluble fraction of cells, and increased CCTα activity in vivo was not detected. Inhibition of the synthesis of fatty acids or their CoA esters by cerulenin or triacsin C respectively following SREBP induction effectively blocked the accompanying elevation in PtdCho synthesis. Thus PtdCho synthesis was driven by increased synthesis of fatty acids or a product thereof. These data show that transcriptional activation of CCTα is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis.

scholarly journals Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis

2013 ◽  
Vol 203 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Michael D. Huber ◽  
Paul W. Vesely ◽  
Kaustuv Datta ◽  
Larry Gerace
Keyword(s):  
Cooperative Control ◽  
Binding Proteins ◽  
Target Genes ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Cellular Cholesterol ◽  
Cholesterol Levels ◽  
Er Retention ◽  
Sterol Regulatory Element ◽  
Diffusional Mobility

Cellular cholesterol levels are controlled by endoplasmic reticulum (ER) sterol sensing proteins, which include Scap and Insig-1. With cholesterol sufficiency, Insig inhibits the activation of sterol regulatory element binding proteins (SREBPs), key transcription factors for cholesterol and fatty acid biosynthetic genes, by associating with Scap–SREBP complexes to promote their ER retention. Here we show that the multimeric ER proteins erlins-1 and -2 are additional SREBP regulators. Depletion of erlins from cells grown with sterol sufficiency led to canonical activation of SREBPs and their target genes. Moreover, SREBPs, Scap, and Insig-1 were physically associated with erlins. Erlins bound cholesterol with specificity and strong cooperativity and responded to ER cholesterol changes with altered diffusional mobility, suggesting that erlins themselves may be regulated by cholesterol. Together, our results define erlins as novel cholesterol-binding proteins that are directly involved in regulating the SREBP machinery. We speculate that erlins promote stability of the SREBP–Scap–Insig complex and may contribute to the highly cooperative control of this system.

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