ANGPTL4 regulates plasma triglyceride levels by inhibiting lipoprotein lipase. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in mesenteric lymph nodes. In mice these pathological events exclusively unfold upon feeding a high saturated fatty acid diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here we show that Angptl4-/- mice fed a diet rich in trans fatty acids develop numerous lipid-filled giant cells in their mesenteric lymph nodes, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a saturated fatty acid-rich diet. In RAW264.7 macrophages the saturated fatty acid palmitate markedly increases markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate have the opposite effect. In conclusion, trans and saturated fatty acids have very distinct biological effects. Furthermore, lipid accumulation in mesenteric lymph nodes is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
Feeding <i>Angptl4</i><sup>-/-</sup> mice <i>trans</i> fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites.
Specimen part, Cell line
View SamplesObjective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range.
Liver adapts mitochondrial function to insulin resistant and diabetic states in mice.
Sex, Specimen part, Treatment
View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
View SamplesGene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways in DSC2 transgenic mice vs. non-transgenic control mice. The mice were analyzed at the age of 3.5 and 13 weeks.
Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling.
Age, Specimen part
View SamplesRNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.
Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.
Cell line, Subject
View SamplesU2AF65 is an essential splicing factor involved in the 3'splice site recognition dureing the first steps of spliceosome assembly. In addition, this protein has nucleocytoplasmic shuttling activity and the Drosophila homologue has been implicated in mRNA export.
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
No sample metadata fields
View SamplesPTB is multifunctional RNA binding protein reported to be involved in splicing, 3' -end processing, stability and translational regulation.
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
No sample metadata fields
View SamplesBlood from subjects with cardioembolic stroke and controls was collected, and the RNA extracted was interrogated and whole genome U133 Affymetrix Arrays. Twenty-three control samples and sixty-nine cardioembolic stroke samples were assayed.
Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.
Specimen part, Subject
View SamplesHuman skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.
Specimen part, Disease, Disease stage
View SamplesDisruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion.
Cardiac Per2 functions as novel link between fatty acid metabolism and myocardial inflammation during ischemia and reperfusion injury of the heart.
Sex, Specimen part
View Samples