Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sex, Age, Specimen part
View SamplesThe brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
Diabetes and insulin in regulation of brain cholesterol metabolism.
Sex, Age, Specimen part
View SamplesGene expression array analysis component. Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with co-regulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining nucleolytic cleavage and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model where the basal occupancy of transcription factors act to prime chromatin and direct inducible transcription factors to select regions in the genome.
Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding.
Sex, Cell line, Treatment, Time
View SamplesControl and Liver Insulin Receptor KO mice (LIRKO) were sacrificed in the non-fasted state. RNA was prepared from liver samples and subjected to expression microarray analysis
Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis.
Specimen part
View SamplesTMAO is gut microbiota dependent metabolite catalyzed by monooxygenase FMO3 from TMA. TMAO is positively assocaited with different metabolic diseases such as diabetes, chronic kidney disease, and atherosclerosis.
Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction.
Sex, Specimen part
View SamplesBy using high-density DNA microarrays, we analyzed the gene-expression profile of liver biopsies from young and aged donors
Impairment of Host Liver Repopulation by Transplanted Hepatocytes in Aged Rats and the Release by Short-Term Growth Hormone Treatment.
Specimen part
View SamplesTamoxifen (Nolvadex) is one of the most widely used and effective therapeutic agent for breast cancer. It benefits nearly 75% of patients with ER-positive breast cancer that receive this drug. Its effectiveness is mainly attributed to its capacity to function as an estrogen receptor (ER) antagonist, blocking estrogen binding sites on the receptor, and inhibiting the proliferative action of the receptor-hormone complex. Although, tamoxifen can induce apoptosis in breast cancer cells via upregulation of pro-apoptotic factors, it can also promote uterine hyperplasia in some women. Thus, tamoxifen as a multi-functional drug could have different effects on cells based on the utilization of effective concentrations or availability of specific co-factors. Evidence that tamoxifen functions as a GPR30 (G-Protein Coupled Receptor 30) agonist activating adenylyl cyclase and EGFR (Epidermal Growth Factor Receptor) intracellular signaling networks, provides yet another means of explaining the multi-functionality of tamoxifen. Here ordinary differential equation (ODE) modeling, RNA sequencing and real time qPCR analysis were utilized to establish the necessary data for gene network mapping of tamoxifen-stimulated MCF-7 cells, which express the endogenous ER and GPR30. The gene set enrichment analysis and pathway analysis approaches were used to categorize transcriptionally upregulated genes in biological processes. Of the 2,713 genes that were significantly upregulated following a 48 h incubation with 250 µM tamoxifen, most were categorized as either growth-related or pro-apoptotic intermediates that fit into the Tp53 and/or MAPK signaling pathways. Collectively, our results display that the effects of tamoxifen on the breast cancer MCF-7 cell line are mediated by the activation of important signaling pathways including Tp53 and MAPKs to induce apoptosis. Overall design: Gene expression analysis between tamoxifen-treated MCF-7 cells and untreated MCF-7 cells.
Tamoxifen-Induced Apoptosis of MCF-7 Cells via GPR30/PI3K/MAPKs Interactions: Verification by ODE Modeling and RNA Sequencing.
Cell line, Subject
View SamplesOocyte developmental potential is progressively obtained as females approach puberty. Therefore, oocytes derived from prepubertal females are less developmentally competent, indicated by decreased embryonic development, compared to oocytes derived from adult females.
Alterations in the transcriptome of porcine oocytes derived from prepubertal and cyclic females is associated with developmental potential.
No sample metadata fields
View SamplesBMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice.
BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity.
Sex, Specimen part
View SamplesExpression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d)
A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development.
No sample metadata fields
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