scholarly journals Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pernille Barkholt ◽  
Kristoffer T. G. Rigbolt ◽  
Mechthilde Falkenhahn ◽  
Thomas Hübschle ◽  
Uwe Schwahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Gene Expression Signature ◽  
Global Gene Expression ◽  
Metabolic Effects ◽  
Expression Of Genes ◽  
Hypothalamic Arcuate Nucleus ◽  
Laser Capture

Abstract The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

scholarly journals Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa

2018 ◽  
Vol 115 (48) ◽  
pp. E11321-E11330 ◽  
Author(s):  
Jie Hou ◽  
Xiaowen Shi ◽  
Chen Chen ◽  
Md. Soliman Islam ◽  
Adam F. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Leaf Tissue ◽  
Global Gene Expression ◽  
Published Data ◽  
Chromosomal Imbalance ◽  
Regulatory Processes ◽  
Expression Of Genes ◽  
Global Impacts

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.

Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression

2006 ◽  
Vol 290 (6) ◽  
pp. R1565-R1569 ◽  
Author(s):  
Kimberly P. Kinzig ◽  
Karen A. Scott ◽  
Jayson Hyun ◽  
Sheng Bi ◽  
Timothy H. Moran
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Time Course ◽  
Arcuate Nucleus ◽  
Central Administration ◽  
Stimulatory Action ◽  
Hypothalamic Arcuate Nucleus ◽  
Ghrelin Receptors ◽  
The Brain

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.

scholarly journals Transcriptome changes reveal the genetic mechanisms of the reproductive plasticity of workers in lower termites

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chenxu Ye ◽  
Humaira Rasheed ◽  
Yuehua Ran ◽  
Xiaojuan Yang ◽  
Lianxi Xing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Mapk Pathway ◽  
Specific Expression ◽  
Expression Of Genes ◽  
Genetic Mechanisms ◽  
Ecological Success ◽  
Reproductive Plasticity

Abstract Background The reproductive plasticity of termite workers provides colonies with tremendous flexibility to respond to environmental changes, which is the basis for evolutionary and ecological success. Although it is known that all colony members share the same genetic background and that differences in castes are caused by differences in gene expression, the pattern of the specific expression of genes involved in the differentiation of workers into reproductives remains unclear. In this study, the isolated workers of Reticulitermes labralis developed into reproductives, and then comparative transcriptomes were used for the first time to reveal the molecular mechanisms underlying the reproductive plasticity of workers. Results We identified 38,070 differentially expressed genes and found a pattern of gene expression involved in the differentiation of the workers into reproductives. 12, 543 genes were specifically upregulated in the isolated workers. Twenty-five signal transduction pathways classified into environmental information processing were related to the differentiation of workers into reproductives. Ras functions as a signalling switch regulates the reproductive plasticity of workers. The catalase gene which is related to longevity was up-regulated in reproductives. Conclusion We demonstrate that workers leaving the natal colony can induce the expression of stage-specific genes in the workers, which leads to the differentiation of workers into reproductives and suggests that the signal transduction along the Ras-MAPK pathway crucially controls the reproductive plasticity of the workers. This study also provides an important model for revealing the molecular mechanism of longevity changes.

scholarly journals Profiling Cellular Processes in Adipose Tissue during Weight Loss Using Time Series Gene Expression

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 525 ◽  
Author(s):  
Samar Tareen ◽  
Michiel Adriaens ◽  
Ilja Arts ◽  
Theo de Kok ◽  
Roel Vink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Dietary Intervention ◽  
Network Biology ◽  
Analysis Tool ◽  
Cellular Processes ◽  
Time Series Gene Expression

Obesity is a global epidemic identified as a major risk factor for multiple chronic diseases and, consequently, diet-induced weight loss is used to counter obesity. The adipose tissue is the primary tissue affected in diet-induced weight loss, yet the underlying molecular mechanisms and changes are not completely deciphered. In this study, we present a network biology analysis workflow which enables the profiling of the cellular processes affected by weight loss in the subcutaneous adipose tissue. Time series gene expression data from a dietary intervention dataset with two diets was analysed. Differentially expressed genes were used to generate co-expression networks using a method that capitalises on the repeat measurements in the data and finds correlations between gene expression changes over time. Using the network analysis tool Cytoscape, an overlap network of conserved components in the co-expression networks was constructed, clustered on topology to find densely correlated genes, and analysed using Gene Ontology enrichment analysis. We found five clusters involved in key metabolic processes, but also adipose tissue development and tissue remodelling processes were enriched. In conclusion, we present a flexible network biology workflow for finding important processes and relevant genes associated with weight loss, using a time series co-expression network approach that is robust towards the high inter-individual variation in humans.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to Oesophageal Adenocarcinoma

2020 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D. Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
A Cell

AbstractOesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths and yet compared to other common cancers, we know relatively little about the underlying molecular mechanisms. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the specific events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies of BO and OAC and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin in OAC cells to directly regulate cell cycle genes specifically in OAC. Our findings have potential prognostic significance as the survival of patients with high expression of KLF5 target genes is significantly lower. We have provided new insights into the gene expression networks in OAC and the mechanisms behind progression to OAC, chiefly the repurposing of KLF5 for novel regulatory activity in OAC.

scholarly journals Trisomy 21 and Down syndrome: a short review

2008 ◽  
Vol 68 (2) ◽  
pp. 447-452 ◽  
Author(s):  
CA. Sommer ◽  
F. Henrique-Silva
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Global Gene Expression ◽  
Short Review ◽  
Complex Disorder ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Chromosome Segments

Even though the molecular mechanisms underlying the Down syndrome (DS) phenotypes remain obscure, the characterization of the genes and conserved non-genic sequences of HSA21 together with large-scale gene expression studies in DS tissues are enhancing our understanding of this complex disorder. Also, mouse models of DS provide invaluable tools to correlate genes or chromosome segments to specific phenotypes. Here we discuss the possible contribution of HSA21 genes to DS and data from global gene expression studies of trisomic samples.

scholarly journals Impact of Chromosome Fusions on 3D Genome Organization and Gene Expression in Budding Yeast

Genetics ◽  
2020 ◽  
Vol 214 (3) ◽  
pp. 651-667 ◽  
Author(s):  
Marco Di Stefano ◽  
Francesca Di Giovanni ◽  
Vasilisa Pozharskaia ◽  
Mercè Gomar-Alba ◽  
Davide Baù ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Nuclear Organization ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Global Gene Expression ◽  
3D Genome ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Chromosome Fusions

The three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remain debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing chromosome fusions. We used computational modeling and single-cell imaging to determine chromosome positions, and integrated these data with genome-wide transcriptional profiles from RNA sequencing. We find that chromosome fusions dramatically alter 3D nuclear organization without leading to strong genome-wide changes in transcription. However, we observe a mild but significant and reproducible increase in the expression of genes displaced away from the periphery. The increase in transcription is inversely proportional to the propensity of a given locus to be at the nuclear periphery; for example, a 10% decrease in the propensity of a gene to reside at the nuclear envelope is accompanied by a 10% increase in gene expression. Modeling suggests that this is due to both deletion of telomeres and to displacement of genes relative to the nuclear periphery. These data suggest that basal transcriptional activity is sensitive to radial changes in gene position, and provide insight into the functional relevance of budding yeast chromosome-level 3D organization in gene expression.

Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays

2001 ◽  
Vol 5 (4) ◽  
pp. 161-170 ◽  
Author(s):  
DAVID GERHOLD ◽  
MEIQING LU ◽  
JIAN XU ◽  
CHRISTOPHER AUSTIN ◽  
C. THOMAS CASKEY ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Metabolism ◽  
Stress Responses ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Effects ◽  
Microarray Technology ◽  
Drug Candidates ◽  
Expression Of Genes

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of ∼90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases ( EHs), UDP-glucuronosyl transferases ( UGTs), glutathione sulfotransferases ( GSTs), sulfotransferases ( STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.

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.

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