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GSE52969
Rattus norvegicus
25 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The endoplasmic reticulum (ER) is the site of secretory lipoprotein production and de novo cholesterol synthesis, yet little is known about how these activities are coordinated with each other, or with the activity of the COPII machinery, which transports ER cargo to the Golgi. The Sar1B component of this machinery is mutated in Chylomicron Retention Disorder, establishing that this Sar1 isoform secures delivery of dietary lipids into the circulation.
Publication Title
The endoplasmic reticulum coat protein II transport machinery coordinates cellular lipid secretion and cholesterol biosynthesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.
Publication Title
Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Bmdm cells were differentiated for 10 days and harvested and culture in six well plate followed by cytokine stimulation after 24 hrs cells were infected with mycobacterium tuberculosis to identify the host factors involved in infection.
Publication Title
IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome.
Publication Title
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
XBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
Publication Title
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Molecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases.
Publication Title
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Publication Title
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background and aim: The Insulin-like growth factor (IGF) axis is increasingly suggested to be involved in fatty liver disease and progression. We identified IGFBP2 as transcriptional regulatory effect network in liver steatosis and conducted a translational approach of its role in liver pathology from mouse to human, and whether it is influenced by conventional clinical intervention that mitigate hepatic steatosis. Methods: Primary hepatocytes from either C57Bl6 controls, alb-SREBP-1c mice with moderate transgene induced hepatic lipid accumulation or aP2-SREBP-1c mice with massive ectopic hepatic lipid accumulation, were analyzed to identify regulatory networks based on differentially regulated hepatic gene expression. In a translational approach, serum of morbidly obese patients with and without diabetes and biopsy-proven NAFLD were used for ELISA-based validation of mouse data. Moreover, sera of patients undergoing intervention were analyzed and correlated to liver fat content. Results: Comparative knowledge-based transcriptome analysis identified IGFBP2 as top score regulatory effect network between moderate and aggravated fatty liver in mouse models. The reduced expression of IGFBP2 in aP2-SREPB-1c progressed fatty liver associated with Igfbp2 promoter hypermethylation. Reduced secretion of IGFBP2 from aP2-SREBP-1c hepatocytes was reflected in the circulation of the animals. In this phenotype, reductions of IGFBP2 were accompanied by reduced fatty acid oxidation and increased methyltransferase and SIRT activity. Physiologically, IGFBP2 has no direct impact on lipid metabolism but might modulate IGF1 action on de novo lipogenesis. In humans, IGFBP2 levels declined from non-obese men to morbidly obese men with NAFLD and NASH. In intervention study reductions in liver fat correlated with restoration of IGFBP2 serum levels to values found in healthy individuals in morbidly obese patients following bariatric surgery. Conclusion: In hepatic metabolism changes of IGFBP2 abundance is connected to lipid metabolism whereas changes in IGFBP2 secretion were directly reflected in the circulation. IGFBP2 serum concentration correlates with the degree of fatty liver, which seems to be related to plasticity of the adipose tissue. These data provide IGFBP2 as a potential non-invasive biomarker for fatty liver disease directly reflecting the degree of impaired liver function with the potential to indicate progressed fatty liver disease.
Publication Title
Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT celldeficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissueresident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissueresident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance.
Publication Title
Natural killer T cells in adipose tissue prevent insulin resistance.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD20 is a clinically validated target for Non-Hodgkins lymphomas and autoimmune diseases. Interactions of CD20 with the B cell receptor (BCR) and components of the BCR signaling cascade have been reported. In this study we show that antibodies against CD20 or activation of the BCR by specific antibodies induce very similar expression patterns of up- or down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa.
Publication Title
Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
Sample Metadata Fields
Cell line, Treatment
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