E-MTAB-6595
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-6595 | ExpressionAtlas | 2018-06-04
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-6595-analysis-methods.tsv | Tabular | |||
| E-MTAB-6595-analytics.tsv | Tabular | |||
| E-MTAB-6595-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-6595-configuration.xml | Xml | |||
| E-MTAB-6595-g2_g1-mvaPlot.png | Other |
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Project description:Quiescent endothelial cells upregulate fatty acid β-oxidation for vasculoprotection via redox homeostasis
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Project description:Little is known about metabolic changes accompanying endothelial cell (EC) quiescence. Nonetheless, when dysfunctional, quiescent ECs (QECs) contribute to multiple cardiovascular diseases. ECs need fatty acid β-oxidation (FAO) for proliferation. Surprisingly, we now report that QECs are not hypo-metabolic, but upregulate FAO >3-fold higher than proliferating ECs (PECs), not to support biomass or energy production, but to sustain the TCA cycle for redox homeostasis through NADPH production. Hence, inhibition of FAO-controlling CPT1A promotes EC dysfunction (anti-fibrinolysis, leukocyte infiltration, barrier disruption) by increasing oxidative stress in CPT1AΔEC mice with endothelial CPT1A loss. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-CoA) induces vasculoprotection against oxidative stress and EC dysfunction in CPT1AΔEC mice, possibly creating therapeutic opportunities. Thus, ECs use FAO for vasculoprotection against their high oxygen (oxidative stress-prone) milieu, and for different metabolic purposes dependent on their proliferation versus quiescence status.
2018-09-12 | E-MTAB-6595 | biostudies-arrayexpress
Project description:Brief summary: Analysis of gene expression in endothelial cells upon contact-inhibition. With this experiments we aimed to identify genes that are associated with the induction of cellular quiescence. Abstract from the associated publication: In contrast to the growing insight in the metabolic reprogramming underlying the angiogenic switch, little is known about the metabolic changes accompanying the quiescence of endothelial cells (ECs). Nonetheless, when dysfunctional, quiescent ECs (QECs) contribute to multiple diseases. Here, we report that QECs are not hypometabolic, but upregulate fatty acid β-oxidation (FAO), not for energy or biomass production, but for redox homeostasis. Hence, inhibition of CPT1a, a rate-controlling step of fatty acid breakdown, promotes a pro-thrombotic and pro-inflammatory signature of QECs by increasing oxidative stress. EC-specific genetic loss similarly elevates oxidative stress in vivo. Compared to proliferating ECs (PECs), QECs switch on a broad “vasculoprotective” metabolic program, involving (i) NAPDH production by the oxidative pentose phosphate pathway (oxPPP) and nicotinamide nucleotide transhydrogenase (NNT), and (ii) prostacyclin synthesis. Molecularly, pro-quiescent Notch signaling elevates FAO by upregulating CPT1a gene transcription. Thus, QECs switch on vasculoprotective metabolic reactions to ensure vascular health.
2018-10-24 | GSE89174 | GEO
Project description:Effect on fatty acid oxidation by etomoxir and etomoxir plus beta-hydroxybutyrate in Glioma-derived Mesenchymal stem cells
2025-01-23 | E-MTAB-8017 | ExpressionAtlas
Project description:We identified rv0158 gene as a major determinant of redox homeostasis in Mtb. Disruption of rv0158 perturbed redox balance in a carbon source-specific manner, promoted killing in response to anti-TB drugs, reduced survival in macrophages, and persistence in mice. RNA sequencing analysis was performed to identify its regulon. The data indicated that rv0158 is required to balance the deployment of fatty acid substrates between lipid anabolism and oxidation.
2023-09-04 | GSE196844 | GEO
Project description:Glucagon signaling blockade protects cardiac microvascular endothelial cells by inhibiting fatty acid β-oxidation and mitochondrial fusion
2021-08-12 | PXD027916 |
Project description:The liver is critical for maintaining systemic energy balance during starvation. To understand the role of hepatic fatty acid β-oxidation on this process, we generated mice with a liver-specific knockout of carnitine palmitoyltransferase 2 (Cpt2L-/-), an obligate step in mitochondrial long-chain fatty acid β-oxidation. Surprisingly, Cpt2L-/- mice survived the perinatal period and a 24hr fast with sufficient blood glucose. The loss of hepatic fatty acid oxidation resulted in a significant loss in circulating ketones that remained unaltered by fasting. Fasting induced serum dyslipidemia, hepatic steatosis and adaptations in hepatic and systemic oxidative gene expression in Cpt2L-/- mice to maintain systemic energy homeostasis. Alternatively, feeding a ketogenic diet resulted in severe hepatomegaly, liver damage and death within one week with a complete absence of adipose triglyceride stores. These data show that hepatic fatty acid oxidation is not required for survival during acute food deprivation but essential for constraining adipocyte lipolysis and regulating systemic catabolism when glucose is limiting. In this dataset, we include the expression data obtained from dissected mouse liver from mice fasted for 24 hours with and without the deletion of carnitine palmitoyltransferase 2 (i.e. hepatocytes unable to beta-oxidize long chain fatty acids in mitochondria). WildType and KnockOut mice were fasted for 24 hours. Three biologic replicates were compared per class, thus six mice.
2016-06-16 | E-GEOD-76079 | biostudies-arrayexpress
Project description:Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator activated receptor (PPAR ) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism. SIRT4 knockout (KO) and wild-type (WT) littermates (male; n 6 per genotype; 7- to 8-month-old littermates) were sacrificed after a 16-h overnight fast. Samples were individually hybridized on Affymetrix Mouse Genome 430 2.0 GeneChips by the Biopolymers Facility (Harvard Medical School).
2014-03-28 | E-GEOD-56321 | biostudies-arrayexpress
Project description:Background: More than 90% mortality of triple negative breast cancer (TNBC) patients are attributed to cancer metastasis with organotropism. Lung is the frequent site of TNBC metastasis. However, the precise mechanism of lung-specific metastasis of TNBC, particularly the driving factors, is not well understood. Methods: RNA sequencing was performed to identify patterns of gene expression associated with lung metastatic behavior using 4T1-LM3, 231-LM3 and their parental cells (4T1-P, 231-P). Expressions of RGCC, encoding the completion 32 protein response protein, were detected in TNBC cells and tissues by qRT-PCR, western blotting and IHC. Kinase activity assay were performed to evaluated PLK1 kinase activity and the amount of phosphorylated AMP-activated protein kinase α2 (AMPKα2). RGCC-mediated metabolism was determined by UHPLC system. Oxidative phosphorylation was evaluated by JC-1 staining and oxygen consumption rate (OCR) assay. Fatty acid oxidation assay, NADPH and ROS was applied to measure the status of RGCC-mediated fatty acid oxidation. The chemical sensitivity of cells was evaluated by CCK8 assay. Results: RGCC is aberrantly upregulated in pulmonary metastatic cells. High level of RGCC is significantly related with lung metastasis rather than other organ metastases. RGCC can effectively promote the kinase activity of PLK1, and activated PLK1 phosphorylates AMPKα2 to facilitate TNBC lung metastasis. Mechanistically, Survival and colonization of TNBC cells in the lungs by upregulating oxidative phosphorylation of mitochondria to obtain more energy and promoting fatty acid oxidation to produce abundant NADPH and sustains redox homeostasis, thus prevents excessive accumulation of potentially detrimental ROS in metastatic tumor cells, ultimately establishing metastases. Importantly, targeting RGCC in combination with paclitaxel/carboplatin effectively suppresses pulmonary metastases of TNBC in a mouse model. Conclusions: The enhanced RGCC is closely associated with lung-specific metastasis of TNBC. RGCC leads to activation of AMPKα2 and downstream signaling through RGCC-driven PLK1 activity to facilitate TNBC lung metastasis, which may determine a potential value of RGCC-driven OXPHOS and fatty acid oxidation as an important therapeutic target.
2023-11-01 | GSE246749 | GEO