Liver of MAT1A WT and MAT1A KO mice treated with placebo or SAMe during 8 weeks
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309410 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
2017-02-02 | GSE77082 | GEO
Project description:Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
2017-02-02 | GSE77079 | GEO
Project description:DNA methylation status of the liver of MAT1A WT and MAT1A KO mice treated with placebo or SAMe during 8 weeks
| PRJNA309409 | ENA
Project description:Gene expression analysis of the liver of MAT1A WT and MAT1A KO mice treated with placebo or SAMe during 8 weeks
| PRJNA309465 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-02 | GSE77084 | GEO
Project description:Mecp2 loss-of-function has been associated with altered gene expression in many tissues. We characterized gene expression changes within the hippocampi of 3 different Mecp2 loss-of-function mouse models. These studies were used to identify transcriptional differences between these mutants when the mice are largely asymptomatic (4 weeks of age) or have developed overt phenotypes (9 weeks). Hippocampal expression data from WT (Mecp2+/y), KO (Mecp2-/y), R270X (Mecp2-/y,R270XTg), and G273X (Mecp2-/y,G273XTg) mice at 4 and 9 weeks At total of 32 microarrays were performed: 4 animals of each genotype at both 4 weeks and 9 weeks of age.
2013-03-22 | E-GEOD-42987 | biostudies-arrayexpress
Project description:scRNAseq of WT and PRMT1-KO microglia during CPZ diet 5 weeks
2022-04-29 | GSE199574 | GEO
Project description:In this proof-of-concept study, we tested whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 participants were exposed to a nauseating stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and gastric activity could be verified. Using state-of-the-art proteomics, 74 differentially regulated proteins were identified as correlates of the placebo effect. Gene ontology (GO) enrichment analyses identified acute-phase proteins and microinflammatory proteins to be involved, and the identified GO signatures predicted day-adjusted scores of nausea indices in the placebo group. We also performed GO enrichment analyses of specific plasma proteins predictable by the experimental factors or their interactions and identified ‘grooming behavior’ as a prominent hit. Finally, Receiver Operator Characteristics allowed to identify plasma proteins differentiating placebo responders from non-responders, comprising immunoglobulins and proteins involved in oxidation reduction processes and complement activation. Plasma proteomics are a promising tool to identify molecular correlates and predictors of the placebo effect in humans.
2020-11-13 | PXD020563 | Pride
Project description:The goal of this study is to compare gene expression differences between WT and tPA KO mice 4 weeks after overexpression of human alpha-synuclein in the substantia nigra
2022-03-28 | E-MTAB-11567 | biostudies-arrayexpress
Project description:The CLARITY trial (NCT00213135) was designed as a double-blind, placebo-controlled study to allow the best comparison of absolute efficacy and safety of oral cladribine in RRMS subjects. 1326 patients with relapsing MS were randomized (1:1:1) to receive cladribine tablets 3.5 mg/kg or 5.25 mg/kg bodyweight or placebo. Gene expression data in whole blood samples at 96 weeks were prepared according to standard Affymetrix protocols Gene expression data in whole blood samples at 96 weeks were available from patients randomized to placebo (n=57), cladribine tablets 3.5 mg/kg (n=62), and cladribine tablets 5.25 mg/kg (n=70).
2023-05-16 | GSE185773 | GEO