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GSE37031
Homo sapiens
15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH.
Publication Title
Molecular interplay between Δ5/Δ6 desaturases and long-chain fatty acids in the pathogenesis of non-alcoholic steatohepatitis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Activation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1 and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner.
Publication Title
Signaling and Immunoresolving Actions of Resolvin D1 in Inflamed Human Visceral Adipose Tissue.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ischemia exists in many diseased tissues including arthritic joints, atherosclerotic plaques and malignant tumors. Macrophages accumulate in these sites and upregulate genes in response to the hypoxia present.
Publication Title
Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.
Publication Title
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here, we analyzed global gene expression changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer using the Affymetrix microarray platform.
Publication Title
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression at baseline, without pro-inflammatory activation, in macrophages.
Publication Title
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression underlying pro-inflammatory activation of macrophage.
Publication Title
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 4 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Analysis of rice leaves (V2 stage) in response to a short treatment with very high CO2 concentration in the dark, using standard atmosphere as control.
Publication Title
High CO2 concentration as an inductor agent to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.
Sample Metadata Fields
Specimen part, Treatment
View Samples