Overconsumption of high-fat diet (HFD) and sugar-sweetened beverages are risk factors for development of obesity, insulin resistance and fatty liver disease. To dissect mechanisms underlying this association, mice were fed chow or HFD with or without addition of fructose- or glucose-supplemented water. There were no physiological differences in mice supplemented with fructose or glucose on chow diet. Despite similar caloric intake, mice on HFD supplemented with fructose developed more pronounced obesity, glucose intolerance and hepatomegaly than glucose-supplemented mice. While both sugars increased Chrebp-?, fructose supplementation uniquely increased Srebp1c and downstream fatty acid synthesis genes resulting in reduced liver insulin signaling, whereas glucose enhanced total Chrebp expression and triglyceride synthesis but was associated with improved hepatic insulin signaling. Metabolomic and RNA sequence analysis confirmed dichotomous effects of fructose and glucose supplementation on liver metabolism in spite of inducing similar amount of hepatic lipid accumulation. Ketohexokinase, the first enzyme of fructose metabolism, was increased in fructose-fed mice and in obese adolescents with steatohepatitis. Knockdown of ketohexokinase-C in liver improved hepatic steatosis and glucose tolerance in fructose-supplemented mice. Thus, fructose is a component of dietary sugar that is uniquely associated with poor metabolic outcomes, while increased glucose intake may be protective.
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Sex, Age, Specimen part, Cell line
View SamplesComparison of expression of Arabidopsis thaliana Col-0 and T-DNA insertion line of RAP2.4a under time dependent light stress by transfer to high light
Meta-analysis of retrograde signaling in Arabidopsis thaliana reveals a core module of genes embedded in complex cellular signaling networks.
Specimen part
View SamplesBilirubin is a potent antioxidant that reduces inflammation and the accumulation of fat. There have been reports of gene responses to bilirubin, which was mostly attributed to its antioxidant function. These RNA-sequencing studies investigated the impact biliverdin, which is rapidly reduced to bilirubin, has on transcriptome responses in human HepG2 hepatocytes in a PPARa-dependent fashion. This investigation reveals that transcriptome responses from the generation of bilirubin are mostly PPARa-dependent, and its antioxidant function regulates a smaller set of genes.
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Sex, Age, Specimen part, Disease, Cell line, Treatment, Race
View SamplesAnalysis of the gene signature of steatosis associated to obesity in hepatocytes of Zucker fa/fa obese rats and their controls; identifying target genes linked to steatosis progression. or Obesity and insulin resistance-associated steatosis can be a non-inflammatory condition affecting hepatocytes or progress to steatohepatitis: a condition that can result in end-stage liver disease. Although molecular events leading to accumulation of lipid droplets in the liver have been identified individually, the complexity of the condition suggested that emergent target would be uncovered by a more comprehensive examination. Then, this study was aimed at establishing a gene signature of steatosis in hepatocytes and at identifying target genes linked to steatosis progression. Using Affymetrix oligonucleotide arrays, we compared transcriptomes of hepatocytes isolated from Zucker "fa/fa" obese rats with three different age-related grades of steatosis with those of their counterpart non-steatotic cells.
A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesTwo of the most prevalent ovarian diseases affecting women's fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease, including decreases in the primordial follicle pool of oocytes that are similar to what is seen in POI, and increases in ovarian cysts that are similar to what is seen in PCOS. In the current study, transgenerational changes to the transcriptome and epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures compared to controls. There was an increase in ovarian disease in transgenerational F3 generation vinclozolin and DDT lineage rats at one year of age compared to F3 generation controls. In purified granulosa cells from 20 day old F3 generation females 164 differentially methylated regions (DMRs) (p<1e-06) were found in the F3 generation vinclozolin lineage, and 293 DMRs (p<1e-06) in the DDT lineage, compared to controls. The long non-coding RNAs (lncRNAs) and small non-coding RNAs (sncRNAs) were found to be differentially expressed in both the vinclozolin and DDT lineages with the sncRNAs having 492 sncRNAs (p<1 x 10-4) in the vinclozolin lineage and 1,085 sncRNAs (p<1 x 10-4) in the DDT lineage. The lncRNAs were differentially expressed with 123 and 51 in the vinclozolin and DDT lineages, respectively (p<1 x 10-4). Differentially expressed mRNAs were found in the vinclozolin lineage at 174 mRNAs (p<1 x 10-4) and the DDT lineage at 212 mRNAs (p<1 x 10-4). These transgenerational epigenetic changes contribute to the dysregulation of the ovary and disease susceptibility that can occur in later life. This suggests that ancestral exposure to toxicants is potentially a major risk factor that must be considered in the molecular etiology of ovarian disease.
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View SamplesTranscriptome analysis of 12 zebrafish tissues
Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database.
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View SamplesTo identify proteins regulated by glucose through changes in their rate of protein synthesis, translational profiling of MIN6 cells acutely incubated at either low or high glucose concentration was performed (i.e. microarray analysis was performed on mRNAs associated with polysomes, as an increase in the association of mRNA with polysomes is indicative of an increase in the rate of initiation step of translation and hence an increase in protein expression) (Johannes et al., 1999; Mikulits et al., 2000).
Distinct glucose-dependent stress responses revealed by translational profiling in pancreatic beta-cells.
Specimen part, Cell line, Compound, Time
View SamplesmicroRNAs play crucial roles in the early development of an organism. However the regulation of transcription through the action of microRNAs during the initial embyonic development has not been studied.
miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio.
Specimen part
View SamplesThe proinflammatory cytokine, TNFalpha is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells. Results indicated that TNFalpha could significantly alter the expression of a significant number of genes; most of them were functionally distributed among molecular functions like catalytic activity, binding, molecular transducer activity, transporter activity, translation and transcription regulator activities or enzyme regulator activity. Also, within genes up-regulated by TNFalpha, several GO terms related to lipid and fat metabolism were significantly overrepresented indicating global dysregulation of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in immunoglobulin receptor activity and IgE binding thereby indicating a compromise in immune defense mechanism(s) apart from those involved the DNA binding and protein binding categories. The interacting network of lipid metabolism, small molecule biochemistry was derived to be significantly affected that correlated well with the top canonical pathway of biosynthesis of steroids and molecular and cellular function of lipid metabolism. All these indicate TNFalpha to be significantly altering the transcriptome profiling within HepG2 cells with genes involved in lipid and steroid metabolism being the most favoured. This study suitably addresses the genes that determine TNFalpha mediated alterations within the hepatocyte mainly the phenotypes of hepatic steatosis and fatty liver that are associated with several hepatic pathological states.
Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
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View SamplesHypobaric Hypoxia Induced Transcriptional profiling of Bovine (Bos indicus)
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Sex, Age, Specimen part, Disease, Disease stage, Subject
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