scholarly journals 2,4-Dinitrotoluene (DNT) Perturbs Yolk Absorption, Liver Development and Lipid Metabolism/Oxygen Transport Gene Expression in Zebrafish Embryos and Larvae

2019 ◽  
Vol 20 (15) ◽  
pp. 3632
Author(s):  
Jianglin Xiong ◽  
Hang Sha ◽  
Hualin Zhou ◽  
Lijuan Peng ◽  
Lingying Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Oxygen Transport ◽  
Target Genes ◽  
Environmental Pollutant ◽  
International Agency ◽  
Liver Development ◽  
Expression Of Genes ◽  
Yolk Absorption ◽  
Carcinogenic Compound

2,4-dinitrotoluene (2,4-DNT) is a common environmental pollutant, and was classified as a group 2B human carcinogenic compound by the International Agency for Research on Cancer. This study determined the toxic effects of 2,4-DNT exposure on zebrafish at the embryo-larvae stage, in terms of organ morphogenesis and the expression pattern of selected target genes related to lipid metabolism and oxygen transportation. The results showed that the 120-h post-fertilization LC50 of 2,4-DNT was 9.59 mg/L with a 95% confidence interval of 8.89–10.44 mg/L. The larvae treated with 2,4-DNT showed toxic symptoms including smaller body, less skin pigment production, yolk malabsorption, and disordered liver development. Further studies on the expression of genes related to lipid transport and metabolism, and respiration indicated that they were significantly affected by 2,4-DNT. It is concluded that 2,4-DNT exposure perturbed liver development and yolk absorption in early-life zebrafish, and disturbed the lipid metabolism /oxygen transport gene expression.

scholarly journals Lipid Stores and Lipid Metabolism Associated Gene Expression in Porcine and Bovine Parthenogenetic Embryos Revealed by Fluorescent Staining and RNA-seq

2020 ◽  
Vol 21 (18) ◽  
pp. 6488
Author(s):  
Arkadiusz Kajdasz ◽  
Ewelina Warzych ◽  
Natalia Derebecka ◽  
Zofia E. Madeja ◽  
Dorota Lechniak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Inner Cell Mass ◽  
Mammalian Species ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Bovine Blastocyst

Compared to other mammalian species, porcine oocytes and embryos are characterized by large amounts of lipids stored mainly in the form of droplets in the cytoplasm. The amount and the morphology of lipid droplets (LD) change throughout the preimplantation development, however, relatively little is known about expression of genes involved in lipid metabolism of early embryos. We compared porcine and bovine blastocyst stage embryos as well as dissected inner cell mass (ICM) and trophoblast (TE) cell populations with regard to lipid droplet storage and expression of genes functionally annotated to selected lipid gene ontology terms using RNA-seq. Comparing the number and the volume occupied by LD between bovine and porcine blastocysts, we have found significant differences both at the level of single embryo and a single blastomere. Aside from different lipid content, we found that embryos regulate the lipid metabolism differentially at the gene expression level. Out of 125 genes, we found 73 to be differentially expressed between entire porcine and bovine blastocyst, and 36 and 51 to be divergent between ICM and TE cell lines. We noticed significant involvement of cholesterol and ganglioside metabolism in preimplantation embryos, as well as a possible shift towards glucose, rather than pyruvate dependence in bovine embryos. A number of genes like DGAT1, CD36 or NR1H3 may serve as lipid associated markers indicating distinct regulatory mechanisms, while upregulated PLIN2, APOA1, SOAT1 indicate significant function during blastocyst formation and cell differentiation in both models.

scholarly journals Genomic dissection of the cytokine-controlled STAT5 signaling network in liver

2008 ◽  
Vol 34 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Atsushi Hosui ◽  
Lothar Hennighausen
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Target Genes ◽  
Global Gene Expression ◽  
Specific Expression ◽  
Partial Explanation ◽  
Downstream Target ◽  
Expression Of Genes ◽  
Global Gene Expression Profiling

Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. Several groups have shown by global gene expression profiling that a cadre of STAT5A/B target genes identify genetic cascades induced by GH and other cytokines. Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. Here we discuss the extent to which studies on global gene expression profiling have fostered a better understanding of the biology behind cytokine-STAT5A/B networks in hepatocytes. We also explore whether this wealth of information on gene activity can be used to further understand the roles of cytokines in liver disease.

scholarly journals Imputed gene associations identify replicable trans-acting genes enriched in transcription pathways and complex traits

2018 ◽  
Author(s):  
Heather E. Wheeler ◽  
Sally Ploch ◽  
Alvaro N. Barbeira ◽  
Rodrigo Bonazzola ◽  
Angela Andaleon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Complex Traits ◽  
Target Gene ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nucleic Acid Binding ◽  
Expression Of Genes ◽  
Gene Associations ◽  
Made In

AbstractRegulation of gene expression is an important mechanism through which genetic variation can affect complex traits. A substantial portion of gene expression variation can be explained by both local (cis) and distal (trans) genetic variation. Much progress has been made in uncovering cis-acting expression quantitative trait loci (cis-eQTL), but trans-eQTL have been more difficult to identify and replicate. Here we take advantage of our ability to predict the cis component of gene expression coupled with gene mapping methods such as PrediXcan to identify high confidence candidate trans-acting genes and their targets. That is, we correlate the cis component of gene expression with observed expression of genes in different chromosomes. Leveraging the shared cis-acting regulation across tissues, we combine the evidence of association across all available GTEx tissues and find 2356 trans-acting/target gene pairs with high mappability scores. Reassuringly, trans-acting genes are enriched in transcription and nucleic acid binding pathways and target genes are enriched in known transcription factor binding sites. Interestingly, trans-acting genes are more significantly associated with selected complex traits and diseases than target or background genes, consistent with percolating trans effects. Our scripts and summary statistics are publicly available for future studies of trans-acting gene regulation.

scholarly journals Perinatal caprine milk oligosaccharides consumption alters maternal and offspring liver gene expression

2020 ◽  
Author(s):  
Caroline Thum ◽  
Wayne Young ◽  
Nicole C Roy ◽  
Warren C McNabb
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Energy Balance ◽  
Visceral Fat ◽  
Control Diet ◽  
Milk Oligosaccharides ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Caprine Milk ◽  
Liver Gene

Abstract Consumption of caprine milk oligosaccharides (CMO) by dams during gestation and lactation, compared to a control diet or a diet supplemented with galacto-oligosaccharides (GOS), was associated with decreased maternal liver weight, increased offspring body weight and length at weaning, and increased offspring visceral fat and serum leptin concentration 30 days after weaning. These changes suggest that dietary CMO alters lipid metabolism, both in dams and offspring. We hypothesized that perinatal CMO intake affected expression of maternal genes in the liver involved in energy metabolism, and programmed pups’ metabolic function leading to increased post-weaning visceral adiposity. To characterise the effects of perinatal consumption of CMOs on maternal and offspring liver gene expression, C57BL/6 mice were fed either a control, CMO, or GOS diet from mating to weaning. From weaning, half of the pups from each maternal group were fed the control diet for 30 days. Microarray analysis was conducted on liver samples from dams and offspring. Differences in the expression of genes involved in lipid metabolism were observed in dams and changes in expression of hepatic genes involved in energy balance and steroid metabolism were observed in pups at weaning. Increased visceral fat was observed in pups 30 days. Perinatal consumption of CMO diet affected infant lipid metabolism, which may be related to altered expression of genes in the liver involved in energy balance and lipid metabolism in dams.

scholarly journals Linoleic acid, α-linolenic acid and enterolactone affect lipid oxidation and expression of lipid metabolism and antioxidant-related genes in hepatic tissue of dairy cows

2017 ◽  
Vol 117 (9) ◽  
pp. 1199-1211 ◽  
Author(s):  
Émilie Fortin ◽  
Richard Blouin ◽  
Jérôme Lapointe ◽  
Hélène V. Petit ◽  
Marie-France Palin
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Oxidative Damage ◽  
Dairy Cows ◽  
Linolenic Acid ◽  
Target Genes ◽  
Culture Media ◽  
Oxidative Damages

AbstractAlthough beneficial effects have been attributed to PUFA supplementation in high-yielding dairy cows, diets rich in PUFA may also increase oxidative stress in tissues such as the liver. To fully exploit the health benefits of PUFA, we believe that the addition of natural antioxidants could help in preventing oxidative damage. Using an in vitro precision-cut liver slices (PCLS) tissue culture system, we investigated the effects of different linoleic acid (LA, n-6):α-linolenic acid (ALA, n-3) ratios (LA:ALA ratio of 4, LA:ALA ratio of 15 and LA:ALA ratio of 25) in the presence or absence of the antioxidant enterolactone (ENL) on (1) the mRNA abundance of genes with key roles in hepatic lipid metabolism, oxidative stress response and inflammatory processes, (2) oxidative damages to lipids and proteins and (3) superoxide dismutase activity in early-lactating dairy cows. The addition of LA and ALA to PCLS culture media increased oxidative damage to lipids as suggested by higher concentrations of thiobarbituric acid reactive substances and increased the expression of nuclear factor erythroid 2-related factor 2 target genes. The addition of ENL was effective in preventing lipid peroxidation caused by LA and ALA. Transcript abundance of sterol regulatory element-binding transcription factor 1 and its lipogenic target genes acetyl-CoA carboxylase α, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) was decreased with LA and ALA, whereas ENL decreased FASN and SCD gene expression. Our results show that addition of LA and ALA to PCLS culture media lowers hepatic lipogenic gene expression and increases oxidative damages to lipids. On the other hand, addition of ENL prevents oxidative damages provoked by these PUFA.

scholarly journals RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis Tadpoles

Endocrinology ◽  
2018 ◽  
Vol 159 (7) ◽  
pp. 2576-2595 ◽  
Author(s):  
Brenda J Mengeling ◽  
Michael L Goodson ◽  
J David Furlow
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Xenopus Laevis ◽  
Animal Studies ◽  
Time Course ◽  
Hormone Receptors ◽  
Target Genes ◽  
Environmental Pollutant ◽  
Luciferase Reporter ◽  
X Receptors

Abstract Appropriate thyroid hormone (TH) signaling through thyroid hormone receptors (TRs) is essential for vertebrate development. Amphibian metamorphosis is initiated and sustained through the action of TH on TRs, which are conserved across vertebrates. TRs heterodimerize with retinoid X receptors (RXRs) on thyroid hormone response elements (TREs) in the genome; however, in most cell line and adult animal studies, RXR ligands do not affect expression of TR target genes. We used a quantitative, precocious metamorphosis assay to interrogate the effects of the RXR agonist bexarotene (Bex) and the RXR antagonist UVI 3003 (UVI) on T3-induced resorption phenotypes in Xenopus laevis tadpoles 1 week postfertilization. Bex potentiated gill and tail resorption, and UVI abrogated T3 action. These results held in transgenic tadpoles bearing a TRE-driven luciferase reporter. Therefore, we used poly-A-primed RNA sequencing transcriptomic analysis to determine their effects on T3-induced gene expression. We also assayed the environmental pollutant tributyltin (TBT), which is an RXR agonist. We found that the proteases that carry out resorption were potentiated by Bex and TBT but were not significantly inhibited by UVI. However, several transcription factors from multiple families (sox4, fosl2, mxd1, mafb, nfib) were all inhibited by UVI and potentiated by Bex and TBT. All required T3 for induction. Time course analysis of gene expression showed that although the agonists could potentiate within 12 hours, the antagonist response lagged. These data indicate that the agonists and antagonist are not necessarily functioning through the same mechanism and suggest that RXR liganding may modulate TH competence in metamorphic signaling.

scholarly journals Gender and age effects on the expression of genes related to lipid metabolism in broiler’s liver

2018 ◽  
Vol 63 (No. 3) ◽  
pp. 103-109
Author(s):  
A. de Souza Khatlab ◽  
A.P. Del Vesco ◽  
E. Gasparino ◽  
A.R. de Oliveira Neto
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Weight Gain ◽  
Feed Intake ◽  
Broiler Chickens ◽  
Fatty Acid Synthase ◽  
Lipid Synthesis ◽  
Gender Effect ◽  
Expression Of Genes ◽  
Gender And Age

Two experiments were conducted to assess gender (Experiment 1) and age (Experiment 2) effects on the expression of genes related to lipid metabolism in broiler chickens. The expression of fatty acid synthase (FAS), apolipoprotein A-I (APOA-I), apolipoprotein B (APOB), adiponectin (ADIPOQ), liver kinase B1 (LKB1), and AMP-activated protein kinase α-1 (AMPKα-1) genes was evaluated by qRT-PCR. In Experiment 1, we observed a gender effect on feed intake, as male broilers presented greater feed intake than females. Female broilers presented greater gene expression of FAS, and lower expression of ADIPOQ and AMPKα-1, than males. A gender effect was not observed for the gene expression of APOA-I, APOB, or LKB1. In Experiment 2, there was a significant age effect on feed intake and weight gain. Broilers 42 days of age presented greater feed intake and weight gain than 21-day-old birds. 21-day-old broilers showed greater expression of APOA-I, ADIPOQ, LKB1, and AMPKα-1, and lower APOB gene expression in the liver than 42-day-old broilers. Age had no effect on FAS gene expression. Our results show that the gender and age could act on the expression of genes related to lipid synthesis, such as FAS and APOB, and also on genes related to lipid oxidation, such as ADIPOQ, LKB1, and AMPK.

scholarly journals Seasonal Consumption of Cherries from Different Origins Affects Metabolic Markers and Gene Expression of Lipogenic Enzymes in Rat Liver: A Preliminary Study

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3643
Author(s):  
Ma. Josefina Ruiz de Azua ◽  
Álvaro Cruz-Carrión ◽  
Begoña Muguerza ◽  
Anna Arola-Arnal ◽  
Manuel Suarez
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Biological Rhythms ◽  
Metabolic Markers ◽  
Hepatic Expression ◽  
Fischer 344 ◽  
Agronomic Practices ◽  
Expression Of Genes ◽  
Different Seasons ◽  
Different Origins

The phytochemical composition of fruits, especially polyphenols, depends on the environmental conditions under which these fruits are cultivated and the agronomic practices followed. Therefore, the consumption of fruits from different origins, with different polyphenol signatures, could have differential effects on health. In addition, recent studies have shown that variation in the biological rhythms due to changes in the photoperiod in the different seasons differentially affect the metabolism in animal models, thus conditioning their response to food consumption. Considering all, this article evaluates the effects of consumption of sweet cherry from different sources, local (LC) and non-local (nLC), on plasma metabolic parameters and the gene expression of key enzymes of lipid metabolism in Fischer 344 rats under photoperiods simulating different seasons. Animals were classified into three photoperiods (L6, L12 and L18) and three treatments (LC, nLC and VH). Both the photoperiod and the treatments significantly affected the evaluated parameters. An effect of the photoperiod on triacylglycerides, non-esterified fatty acids and the mRNA concentration of crucial enzymes from the hepatic lipid metabolism was observed. Furthermore, the consumption of fruit in L12 lowered blood glucose, while the different treatments affected the hepatic expression of genes related with lipidic enzymes.

scholarly journals Pathophysiological Potentials of NRF3-Regulated Transcriptional Axes in Protein and Lipid Homeostasis

2021 ◽  
Vol 22 (23) ◽  
pp. 12686
Author(s):  
Tsuyoshi Waku ◽  
Akira Kobayashi
Keyword(s):  
Gene Expression ◽  
Leucine Zipper ◽  
Target Genes ◽  
Proteasome Inhibition ◽  
Cancer Development ◽  
Lipid Homeostasis ◽  
Cancer Cell Growth ◽  
Basic Leucine Zipper ◽  
Cycle Arrest ◽  
Expression Of Genes

NRF3 (NFE2L3) belongs to the CNC-basic leucine zipper transcription factor family. An NRF3 homolog, NRF1 (NFE2L1), induces the expression of proteasome-related genes in response to proteasome inhibition. Another homolog, NRF2 (NFE2L2), induces the expression of genes related to antioxidant responses and encodes metabolic enzymes in response to oxidative stress. Dysfunction of each homolog causes several diseases, such as neurodegenerative diseases and cancer development. However, NRF3 target genes and their biological roles remain unknown. This review summarizes our recent reports that showed NRF3-regulated transcriptional axes for protein and lipid homeostasis. NRF3 induces the gene expression of POMP for 20S proteasome assembly and CPEB3 for NRF1 translational repression, inhibiting tumor suppression responses, including cell-cycle arrest and apoptosis, with resistance to a proteasome inhibitor anticancer agent bortezomib. NRF3 also promotes mevalonate biosynthesis by inducing SREBP2 and HMGCR gene expression, and reduces the intracellular levels of neural fatty acids by inducing GGPS1 gene expression. In parallel, NRF3 induces macropinocytosis for cholesterol uptake by inducing RAB5 gene expression. Finally, this review mentions not only the pathophysiological aspects of these NRF3-regulated axes for cancer cell growth and anti-obesity potential but also their possible role in obesity-induced cancer development.

scholarly journals Combined Analysis of Expression Profiles in a Mouse Model and Patients Identified BHMT2 as a New Regulator of Lipid Metabolism in Metabolic-Associated Fatty Liver Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongqiang Ma ◽  
Zhi Tan ◽  
Qiang Li ◽  
Wenling Fan ◽  
Guangshun Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Differentially Expressed Genes ◽  
Fatty Liver Disease ◽  
Target Genes ◽  
Differentially Expressed ◽  
Overlapping Genes ◽  
Geo Database

Metabolic associated fatty liver disease (MAFLD) is associated with obesity, type 2 diabetes mellitus, and other metabolic syndromes. Farnesoid X receptor (FXR, NR1H4) plays a prominent role in hepatic lipid metabolism. This study combined the expression of liver genes in FXR knockout (KO) mice and MAFLD patients to identify new pathogenic pathways for MAFLD based on genome-wide transcriptional profiling. In addition, the roles of new target genes in the MAFLD pathogenic pathway were also explored. Two groups of differentially expressed genes were obtained from FXR-KO mice and MAFLD patients by transcriptional analysis of liver tissue samples. The similarities and differences between the two groups of differentially expressed genes were analyzed to identify novel pathogenic pathways and target genes. After the integration analysis of differentially expressed genes, we identified 134 overlapping genes, many of which have been reported to play an important role in lipid metabolism. Our unique analysis method of comparing differential gene expression between FXR-KO mice and patients with MAFLD is useful to identify target genes and pathways that may be strongly implicated in the pathogenesis of MAFLD. The overlapping genes with high specificity were screened using the Gene Expression Omnibus (GEO) database. Through comparison and analysis with the GEO database, we determined that BHMT2 and PKLR could be highly correlated with MAFLD. Clinical data analysis and RNA interference testing in vitro confirmed that BHMT2 may a new regulator of lipid metabolism in MAFLD pathogenesis. These results may provide new ideas for understanding the pathogenesis of MAFLD and thus provide new targets for the treatment of MAFLD.

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