scholarly journals Butyrate enemas upregulate Muc genes expression but decrease adherent mucus thickness in mice colon

2009 ◽  
pp. 111-119 ◽  
Author(s):  
E Gaudier ◽  
M Rival ◽  
M-P Buisine ◽  
I Robineau ◽  
Ch Hoebler
Keyword(s):  
Gene Expression ◽  
Layer Thickness ◽  
Specific Effect ◽  
Fold Increase ◽  
Mucus Layer ◽  
Protective Function ◽  
Genes Expression ◽  
Mucus Gel ◽  
Muc Genes

Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an endproduct of carbohydrate fermentation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not.

Abstract 41: Explant-Derived Cells from Chronic Heart Failure Activated Endothelial-Mesenchymal Transition and Attenuated Pluripotency Genes Expression

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Liudmila Zakharova ◽  
Hikmet Nural ◽  
Mohamed A Gaballa
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Smooth Muscle Actin ◽  
Fold Increase ◽  
Gene Expressions ◽  
Mesenchymal Transition ◽  
Cell Outgrowth ◽  
Pluripotency Genes

Cardiac progenitor cells are generated from atria explants; however the cellular origin and the mechanisms of cell outgrowth are unclear. Using transgenic tamoxifen-induced Willms tumor 1 (Wt1)-Cre/ERT and Cre-activated GFP reporter mice, we found approximately 40% of explant-derived cells and 74% of explant-derived c-Kit+ cells originated from the epicardium. In atria from sham hearts, Wt1+ cells were located in a thin epicardial layer, while c-Kit+ cells were primarily found within both the sub-epicardium and the myocardium, albeit at low frequency. No overlap between c-Kit+ and Wt1+ cells was observed, suggesting that epicardial Wt1+ cells do not express c-Kit marker in vivo, but more likely the c-Kit marker was acquired in culture. Compared with 4 days in culture, at day 21 we observed 7 folds increase in Snail gene expression; 32% increase in α-smooth muscle actin (SMA) marker, and 30% decrease in E-cadherin marker, suggesting that the explant-derived cells underwent epithelial to mesenchymal transition (EMT) in vitro. Cell outgrowths released TGF-β (1036.4 ± 1.18 pm/ml) and exhibited active TGF-β signaling, which might triggered the EMT. Compared to shams, CHF cell outgrowths exhibited elevated levels of EMT markers, SMA (49% vs. 34%) and Snail (2 folds), and reduced level of Wt1 (11% vs. 22%). In addition, CHF cell outgrowths had two folds increase in Pai1 gene expression, a direct target of TGF-β signaling. In c-Kit+ cells derived from CHF explants, Nanog gene expression was 4 folds lower and Sox 2 was 2 folds lower compared with cells from shams. Suppression of EMT in cell outgrowth increased the percentage of c-Kit+ and Wt1+ cells by 17%, and 15%, respectively. Also suppression of EMT in c-Kit+ cells resulted in 4 folds increase in Nanog and 3 fold increase in Sox2 gene expressions. Our results showed that CHF may further exuberates EMT while diminishes the re-activation of pluripotency genes. Thus, EMT modulation in CHF is a possible strategy to regulate both the yield and the pluripotency of cardiac-explant-derived progenitor cells.

Hyperglycemia modulates angiotensinogen gene expression

2001 ◽  
Vol 281 (3) ◽  
pp. R795-R802 ◽  
Author(s):  
Ilan Gabriely ◽  
Xiao Man Yang ◽  
Jane A. Cases ◽  
Xiao Hui Ma ◽  
Luciano Rossetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Biosynthetic Pathway ◽  
Fold Increase ◽  
Suppressive Effect ◽  
Sprague Dawley ◽  
Hexosamine Biosynthetic Pathway ◽  
Obese Rats ◽  
Agt Gene

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (∼300 g) and obese (∼450 g) Sprague-Dawley rats in four clamp studies ( n= 3/group), creating physiological hyperinsulinemia (∼60 μU/ml, by an insulin clamp), hyperglycemia (∼18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 μmol · kg−1 · min−1) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats ( P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient “pulses” may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.

scholarly journals Regulation of interleukin 2 gene expression by CD28 costimulation in mouse T-cell clones: both nuclear and cytoplasmic RNAs are regulated with complex kinetics.

1995 ◽  
Vol 15 (6) ◽  
pp. 3197-3205 ◽  
Author(s):  
S W Umlauf ◽  
B Beverly ◽  
O Lantz ◽  
R H Schwartz
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 2 ◽  
Specific Effect ◽  
Fold Increase ◽  
Cell Receptor ◽  
Cd28 Costimulation ◽  
Reporter Assays ◽  
Tcr Signalling

T-cell receptor (TCR) signalling is required to induce expression of the interleukin 2 (IL-2) gene in mouse T cells. Additional costimulation through CD28 augments IL-2 production by 30- to 100-fold. Using IL-2 RNA accumulation and transcription reporter assays, we have addressed potential mechanisms of CD28 regulation at various time points of stimulation. The kinetic regulation of IL-2 mRNA by TCR and CD28 signals is complex: (i) at the earliest detectable time point, CD28 signalling causes a 20-fold increase compared with TCR signalling alone; (ii) both groups rapidly accumulate mRNA for the first 4 h; (iii) IL-2 mRNA then disappears from cells stimulated through the TCR alone but plateaus or increases slightly in cells costimulated through CD28; and (iv) after 8 h, the mRNA disappears in cultures with the anti-CD28 antibody. Transcription reporter assays did not show a specific effect of CD28 signalling on IL-2 enhancer driven transcription. This was true for either a 353- or a 1.9-kb enhancer, over a broad range of kinetics and TCR occupancy, and with several TCR signal mimics. The early component of CD28 costimulation is nuclear, however, since the initial enhancement of mRNA is also found in unspliced IL-2 RNA. Between 2 and 6 h, there is a marked difference in the rates of decay of IL-2 mRNA in the presence and absence of the CD28 signalling. Rapid decay of IL-2 mRNA commences after 8 h even in the presence of CD28 signals, although the decay occurs at a rate slower than that seen after 4 h of anti-TCR stimulation alone. This complexity suggests the existence of two interesting molecular mechanisms by which CD28 costimulates lymphokine gene expression.

3 IN VITRO MATURATION ALTERS GENE EXPRESSION IN MOUSE OOCYTES

2008 ◽  
Vol 20 (1) ◽  
pp. 82
Author(s):  
M. Paczkowski ◽  
C. Bidwell ◽  
D. Spurlock ◽  
J. Waddell ◽  
R. L. Krisher
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Dna Methyltransferase ◽  
In Vitro Maturation ◽  
Fold Increase ◽  
Developmental Competence ◽  
Differentially Expressed ◽  
Dna Methyltransferase 1

The in vitro culture environment significantly impacts nuclear maturation, fertilization, embryonic development, and epigenetic competence; however, our knowledge of the effects of in vitro maturation on oocyte developmental competence, and specifically cytoplasmic maturation, is limited. The objective of this experiment was to identify alterations in the transcriptome of oocytes matured in vitro compared to those matured in vivo that correlate to developmental competence. Immature oocytes were collected from Day 26 and 7-8-week-old B6D2F1 mice 48 h post-pregnant mare serum gonadotropin (PMSG) administration and matured for 16 h in Gmat supplemented with 0.5 mm citric acid, 0.5 mm cysteamine, 100 ng mL–1 epidermal growth factor (EGF), 0.05% insulin-transferrin-selenium (ITS; v/v), 0.01% recombumin (v/v) and 2 mg mL–1 fetuin. In vivo-matured oocytes from females of the same ages were collected from the oviducts 62 h post-PMSG and 14 h post-hCG and mating to vasectomized males. In vivo- and in vitro-matured oocytes were identified visually by the presence of the first polar body. Mature oocytes were pooled into three groups of 150 oocytes per treatment and lysed; poly A+ RNA was extracted. Samples were processed through two cycles of linear amplification and hybridized to the GeneChip� Mouse Genome 430 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA), with three arrays per treatment. Microarray data were sorted and filtered to include genes that were classified as having two present calls per treatment. The data were then normalized to the chip median and analyzed using a one-way analysis of variance; the level of significance was calculated at P < 0.01. In total, 2.17% (482/22170) and 1.61% (358/22170) of genes were differentially expressed between in vitro- and in vivo-matured oocytes in Day 26 and 7–8-week-old mice, respectively. However, 72.82% (351/482) and 67.87% (243/358) of differentially expressed genes had increased abundance in the in vitro- and in vivo-matured oocytes, respectively. Transcripts involved in gene expression, cellular growth and proliferation, and cellular development were increased in in vivo-matured oocytes from both age groups compared to those matured in vitro. Cell death was one of the higher ranking functional groups increased in the 7–8-week-old in vitro-matured oocytes compared to the 7–8-week-old in vivo-matured oocytes. Specific genes altered by in vitro maturation conditions in Day 26 oocytes were DNA methyltransferase 1 (>7-fold increase in vivo), caspase 8 (>4-fold increase in vivo), and eukaryotic translation initiation factor 1B (>4-fold increase in vivo). DNA methyltransferase 1 and ubiquitin-conjugating enzyme E2T were significantly increased in in vivo-matured 7–8-week-old oocytes (>3-fold and >5-fold, respectively). These results indicate that gene expression is altered in oocytes matured in vitro compared to those matured in vivo. Based on the functional annotations of genes differentially expressed, dysregulation of gene expression in the oocyte resulting in altered DNA methylation and an up-regulation in cell death pathways are potential developmental mechanisms influenced by in vitro culture conditions that correlate to reduced embryonic developmental potential.

IL-2 Therapy Promotes the Expansion of Human CD4+CD25+ Regulatory T Cells and Selectively Upregulates the Expression of FOXP3 in T Cells In Vivo.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1257-1257
Author(s):  
Emmanuel Zorn ◽  
Erik A. Nelson ◽  
Mehrdad Mohseni ◽  
Despina Litsa ◽  
Haesook Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Regulatory T Cells ◽  
Nk Cells ◽  
Quantitative Pcr ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Foxp3 Expression ◽  
Prolonged Administration

Abstract Recombinant IL-2 has been used extensively in clinical trials to enhance a wide range of immune responses. Overall this strategy has had limited efficacy. Recent evidence suggests that IL-2 plays a key role in the generation and maintenance of CD4+CD25+ regulatory T cells (Treg) in vivo. In our study, we investigated the effect of prolonged administration of recombinant IL-2 on Treg in vivo. In a retrospective analysis, we first examined CD4+CD25+ Treg in blood samples collected from 21 cancer patients before and after they started continuous treatment with IL-2 at a dose of 2 X 105 U/m2/day for 3 months. Nine patients received IL-2 beginning 3 months after CD6 T cell depleted allogeneic bone marrow transplantation (BMT) for CML. The remaining 12 patients received IL-2 as treatment for advanced solid tumors. Overall toxicity was minimal and none of the transplant patients developed GVHD following IL-2 administration. Previous reports demonstrated that this prolonged treatment with low-dose IL-2 resulted in the expansion of CD56+CD3− NK cells in peripheral blood. Further analysis showed that 15 patients exhibited an expansion of Treg in peripheral blood 26 to 77 days after beginning IL-2 as demonstrated by an increase in the CD4+CD25+/CD3+ ratio (median fold increase 2.68; range 1.3 to 59). Three patients had no significant change and 3 patients demonstrated a decreased Treg/CD3 ratio. Using RNA from the same samples we also measured the expression of the Treg specific transcription factor FOXP3 by quantitative PCR. Nineteen of 21 patients showed a marked increase in FOXP3 expression following IL-2 treatment (8.38 median fold increase; range 1.4 to 41.5). Only 2 of 21 patients had lower FOXP3 expression after IL-2 administration. Since IL-2 treatment resulted in the expansion of NK cells as well as Treg, we purified CD56+CD3− NK cells and CD4+ T cells from patient samples collected post-IL-2 treatment, and measured FOXP3 gene expression in both subsets. In 4 analyzed cases, FOXP3 was selectively expressed in CD4+ T cells. Further analysis of purified Treg and NK cells incubated with IL-2 in vitro confirmed that FOXP3 expression was selectively induced in Treg, and also suggested that the in vivo increase in FOXP3 expression resulted from both Treg expansion and up-regulation of gene expression at the single cell level. To study the duration of the IL-2 effect, we analyzed additional samples collected 2 to 8 months after IL-2 treatment was completed. Nine of 10 patient samples tested showed a decrease in the CD4+CD25+/CD3+ ratio (1.39 median fold decrease; range 1.13 to 15.02). Using quantitative PCR, expression of FOXP3 decreased for 6 of 8 patients tested (10.76 median fold decrease; range 1.22 to 88.31). These results indicate that prolonged administration of IL-2 promotes the expansion of CD4+CD25+ Treg in vivo and also has a direct effect on FOXP3 expression. Although administration of IL-2 has previously been used to enhance T and NK cell responses, this study demonstrates that IL-2 therapy predominantly reinforces the regulatory component of the immune response, and may provide a means for controlling immune reactions in vivo.

scholarly journals Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 470-475 ◽  
Author(s):  
J L Newton ◽  
N Jordan ◽  
L Oliver ◽  
V Strugala ◽  
J Pearson ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Structural Changes ◽  
Endoscopic Biopsy ◽  
Gastric Atrophy ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Mucus Gel ◽  
Mucus Barrier ◽  
H Pylori

Background—It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial.Aims—To clarify the effects of H pylori infection on the mucus gel barrier in vivo.Methods—Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pyloriinfection.Results—There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness betweenH pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) μm, 106 (30) μm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) μm, p=0.03) compared with those without atrophy.Conclusions—A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

scholarly journals c-Myc inhibition is critical for HSC expansion and Rad51 expression

2018 ◽  
Author(s):  
Merve Aksoz ◽  
Esra Albayrak ◽  
Galip Servet Aslan ◽  
Raife Dilek Turan ◽  
Lamia Yazgi Alyazici ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Fold Increase ◽  
Hematopoietic Stem ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Nos Inhibitor ◽  
Kinetics Of

c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to downregulation of glycolytic and cyclin-dependent kinase inhibitor (CDKI) gene expression ex vivo and in vivo. In addition, c-Myc inhibition upregulates major HDR modulator Rad51 expression in hematopoietic cells. Besides, c-Myc inhibition does not alter proliferation kinetics of endothelial cells, fibroblasts or adipose derived mesenchymal stem cells, however; it limits bone marrow derived mesenchymal stem cell proliferation. We further demonstrate that a cocktail of c-Myc inhibitor 10074-G5 along with tauroursodeoxycholic acid (TUDCA) and i-NOS inhibitor L-NIL provides a robust HSC maintenance and expansion ex vivo as evident by induction of all stem cell antigens analyzed. Intriguingly, the cocktail of c-Myc inhibitor 10074-G5, TUDCA and L-NIL improves HDR related gene expression. These findings provide tools to improve ex vivo HSC maintenance and expansion, autologous HSC transplantation and gene editing through modulation of HSC glycolytic and HDR pathways.

scholarly journals Dynamic Changes in Function and Proteomic Composition of Extracellular Vesicles from Hepatic Stellate Cells during Cellular Activation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 290 ◽  
Author(s):  
Xinlei Li ◽  
Ruju Chen ◽  
Sherri Kemper ◽  
David R Brigstock
Keyword(s):  
Gene Expression ◽  
Hepatic Stellate Cells ◽  
Fold Increase ◽  
Stellate Cells ◽  
Extracellular Vesicle ◽  
Fine Tuning ◽  
Shared Identity ◽  
Cellular Source

During chronic liver injury, hepatic stellate cells (HSC) undergo activation and are the principal cellular source of collagenous scar. In this study, we found that activation of mouse HSC (mHSC) was associated with a 4.5-fold increase in extracellular vesicle (EV) production and that fibrogenic gene expression (CCN2, Col1a1) was suppressed in Passage 1 (P1; activated) mHSC exposed to EVs from Day 4 (D4; relatively quiescent) mHSC but not to EVs from P1 mHSC. Conversely, gene expression (CCN2, Col1a1, αSMA) in D4 mHSC was stimulated by EVs from P1 mHSC but not by EVs from D4 mHSC. EVs from Day 4 mHSC contained only 46 proteins in which histones and keratins predominated, while EVs from P1 mHSC contained 337 proteins and these were principally associated with extracellular spaces or matrix, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes and chaperones. EVs from the activated LX-2 human HSC (hHSC) line also promoted fibrogenic gene expression in D4 mHSC in vitro and contained 524 proteins, many of which shared identity or had functional overlap with those in P1 mHSC EVs. The activation-associated changes in production, function and protein content of EVs from HSC likely contribute to the regulation of HSC function in vivo and to the fine-tuning of fibrogenic pathways in the liver.

Assessment of PD-1 expression in human resting and activated natural killer cells and murine tumor models.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 36-36
Author(s):  
Sean J. Judge ◽  
Cordelia Dunai ◽  
Ian R. Sturgill ◽  
Kevin M. Stoffel ◽  
William J. Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Ex Vivo ◽  
Fold Increase ◽  
Wild Type ◽  
Immunodeficient Mice

36 Background: Blockade of the PD-1/PD-L1/2 axis has revolutionized cancer therapy. Although reinvigorated PD-1+ T cells are the main effectors in the response to checkpoint blockade, the contribution of Natural Killer (NK) cells to PD-1/PD-L1 inhibition is under debate. While PD-1 has been identified on NK cells, this appears to be restricted to small populations under limited conditions. We sought to evaluate the extent of PD-1 expression in mouse and human resting and activated NK cells. Methods: Human NK cells were isolated from healthy donor PBMCs and cancer patients. Ex vivo activation and proliferation techniques included recombinant human cytokine and feeder line co-culture. Murine NK cells were isolated from splenocytes, and PBMCs from wild type and immunodeficient mice. We assessed NK cell surface markers and intracellular cytokine by flow cytometry, and gene expression by quantitative RT-PCR. Results: Over 21-days of ex vivo expansion, expression of PD-1 or PD-L1 on human NK cells was < 1% at all time points, while TIGIT+ expression increased to > 85%. Conversely, ConA stimulation of T cells increased PD-1 expression with no change in TIGIT expression. QRT-PCR demonstrated absent PD-1 expression in purified NK cells compared to a 5-fold increase in PD-1 gene expression in ConA stimulated PBMCs. PD-1/PD-L1 was also < 1% in the NK92 cell line and < 2.5% in peripheral CD56+CD3- NK cells from patients with soft tissue sarcoma (STS). NK cells from digested freshly resected STS show variable PD-1 ( < 10%) and minimal PD-L1 ( < 1%) expression with a small, but measurable population of intra-tumoral NK cells (1% of immune cells). In vivo mouse studies showed < 5% PD-1+ NK cells in spleen and tumor of CT26 tumor-bearing mice, while PD-L1+ NK cells increased in frequency from spleen (5-35%) to tumor (40-95%) in both wild type BALB/C and SCID mice. Conclusions: In contrast to prior studies, we did not observe a substantial PD-1+ population on human or murine NK cells after multiple activation strategies compared to T cells. Contrary to its application in T cells, our data suggest that PD-1 is not a useful marker for NK cell exhaustion/dysfunction. PD-L1 on NK cells may represent an important link between NK and T cell immunotherapy.

Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue

2004 ◽  
Vol 287 (3) ◽  
pp. E424-E430 ◽  
Author(s):  
Zhibin He ◽  
Tao Jiang ◽  
Zhuowei Wang ◽  
Moshe Levi ◽  
Jinping Li
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Mrna Level ◽  
Fold Increase ◽  
Response Element ◽  
Element Binding Protein ◽  
Rat Adipose Tissue

Carbohydrate response element-binding protein (ChREBP) is a rat homolog of human Williams-Beuren syndrome region 14 and a member of the basic helix-loop-helix leucine zipper transcription factor family. Its activation was found to be inducible by carbohydrate in the liver nuclear extracts from rats fed a high-sucrose diet. ChREBP is able to bind to the carbohydrate response element on the promoter of L-type pyruvate kinase and initiate the gene transcription. The detailed expression profile and transcriptional regulation of the ChREBP gene in adipocytes have not been characterized. In the present study, we provide evidence showing that 1) the ChREBP gene is expressed in differentiated 3T3-L1 adipocytes and rat adipose tissue; 2) insulin, glucose, and the antidiabetic agent troglitazone can significantly upregulate the gene expression of ChREBP in 3T3-L1 adipocytes, whereas free fatty acids suppress its expression in this cell type; 3) fasting followed by refeeding with a high-carbohydrate diet resulted in a 10-fold increase of ChREBP mRNA level in rat adipose tissue; and 4) ChREBP expression in adipose tissue is not significantly affected by the diabetic state. Taken together, the results we present are consistent with the idea that ChREBP is an important modulator of adipocyte biology and that its expression in adipose tissue is subject to combined regulation by glucose and insulin in vivo. The induction of ChREBP may serve as a novel pharmacological pathway for troglitazone-mediated hypoglycemic effects in vivo.

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