Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA132695 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The ER-resident prote in fat-inducing transcript 2 (FIT2) catalyzes acyl-CoA cleavage in vitro, and in cells is required for endoplasmic reticulum (ER)homeostasis and normal lipid storage. The gene encoding FIT2 is essential for viability of mice and worms. Whether FIT2 acts as anacyl-CoA diphosphatase in vivo and how this activity affects liver, where the protein was discovered,is unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. FIT2-LKO mice had increased triglyceride (TG) content in liver when fed a chow diet, compared with control littermates due in part to impaired secretion of TG-rich lipoproteins and reduced capacity for fatty acid oxidation. Challenging FIT2-LKO mice with a high-fat diet to increase FIT2 acyl-CoA substrates worsened hepatic ER stress and liver injury, yet unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings show that FIT2 acts as anacyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in murine liver
2023-05-10 | PXD033884 | Pride
Project description:Nudix hydrolase 7 (NUDT7) is a peroxisomal (acyl-)CoA-degrading enzyme that is highly expressed in the liver. We previously showed that liver-specific NUDT7 overexpression affects peroxisomal lipid metabolism, but does not prevent the increase in total liver CoA levels that occurs with fasting. Herein, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low fat diet, but only in males fed a western diet does the lack of NUDT7 increase total liver CoA levels. This effect is driven by the accumulation of medium-chain dicarboxylic acyl-CoAs, which are products of the oxidation of dicarboxylic fatty acids in the peroxisomes. We also show that, under conditions of increased cholesterol intake and elevated bile acid synthesis, Nudt7 deletion increases the production of tauro-muricholic acids, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion. Collectively, our findings reveal a key role for NUDT7 in the regulation of the final products of bile acid synthesis and dicarboxylic fatty acid oxidation
2022-11-25 | GSE207914 | GEO
Project description:The ER-resident protein fat-inducing transcript 2 (FIT2) catalyzes acyl-CoA cleavage in vitro and is required for endoplasmic reticulum (ER) homeostasis and normal lipid storage in cells. The gene encoding FIT2 is essential for the viability of mice and worms. Whether FIT2 acts as an acyl-CoA diphosphatase in vivo and how this activity affects liver, where the protein was discovered, are unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice fed a chow diet exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. These mice also had more triglycerides in their livers than control littermates due, in part, to impaired secretion of triglyceride-rich lipoproteins and reduced capacity for fatty acid oxidation. Challenging FIT2-LKO mice with a high-fat diet worsened hepatic ER stress and liver injury, but unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings support the model that FIT2 acts as an acyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in murine liver.
2022-09-17 | ST002303 | MetabolomicsWorkbench
Project description:Acyl-CoA synthetase medium-chain family member 3 (ACSM3) is one member of ACSM family and localized on the outer membrane of mitochondria, which catalyzes the activation of medium-chain (C4-C14) length FAs and xenobiotic carboxylic acids. We found that ACSM3 was lower expressed in the metabolic syndrome (MetS) patients and mice. ACSM3 mainly expressed in the liver. We speculated that ACSM3 deficiency may participated in the MetS progression and then constructed Acsm3 global knockout mice (C57BL/6J background) by CRISPR/Cas9 system. The knockout mice exhibited profound depletion of Acsm3 expression in liver extracts. Male mice are more sensitive to diet-induced MetS than female mice, and thus male mice were used in this study. The phenotype of Acsm3 knockout mice was analyzed with wild type littermates as controls. 12 weeks, livers from three male Acsm3 knockout mice and three male control mice were removed for RNA sequencing.
2023-11-12 | GSE247290 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived cerebellar transcriptome profiling (RNA-seq) to determine age-relatined impact of acsl6 deficiency on brain transcriptome profiles. Methods: Cerebellar mRNA profiles of 2-month and 18-month control and long-chain acyl-coa synthetase 6-knockout (Acsl6) mice were generated and sent to Genewiz for RNAseq analysis Results: Using an optimized data analysis workflow, we mapped about 3,451,694,754 sequence reads total and ~25-45 million reads per sample of which ~98% were mapped to the mouse genome. Conclusions: Our study represents the first detailed analysis of cerebellar transcriptomes of Acsl6 knockout mice, compated to controls, at young and old ages.
2021-05-27 | GSE175571 | GEO
Project description:Liver tumors had high levels of histone acetylation. Nrf2 knockout mice developed fewer tumors than Nrf2 wild-type mice. The mechanistic study found that Nrf2 knockout reduced the generation of acetyl CoA from impaired glycolysis, TCA cycle, and fatty acid metabolism. Acetyl CoA is the substrate for protein acetylation including histone acetylation. Here we determined the genome-wide distribution of AcH3K27. We found that Nrf2 through regulating acetyl CoA production affects histone acetylation (AcH3K27) to modulate the expression of genes, whose products were involved in the glycolysis, TCA cycle, fatty acid metabolism, and oncogenic Myc/mTor signaling. Our findings supported an Nrf2-integrated metabolic, epigenetic and oncogenic signaling in driving liver tumor development.
2023-03-20 | GSE227068 | GEO
Project description:Floodings already have a nearly 60% share in the worldwide damage to crops provoked by natural disasters. Climate change will cause plants to be even more frequently exposed to oxygen limiting conditions (hypoxia) in the near future due to heavy precipitation and concomitant waterlogging or flooding events in large areas of the world. Although the homeostatic regulation of adaptive responses to low oxygen stress in plants is well described, it remained unknown by which initial trigger the molecular response to low-oxygen stress is activated. Here, we show that a hypoxia-induced decline of the ATP level of the cell reduces LONG-CHAIN ACYL-COA SYNTHETASE (LACS) activity, which leads to a shift in the composition of the acyl-CoA pool. High oleoyl-CoA levels release the transcription factor RELATED TO APETALA 2.12 (RAP2.12) from its interaction partner ACYL-COA BINDING PROTEIN (ACBP) at the plasma membrane to induce low oxygen-specific gene expression. We show that different acyl-CoAs provoke unique molecular responses revealing a novel role as cellular signalling component also in plants. In terms of hypoxia signalling, dynamic acyl-CoA levels integrate the cellular energy status into the oxygen signalling cascade with ACBP and RAP2.12 being the central hub. The conserved nature of the ACBP:RAP2.12 module in crops and the novel mechanistic understanding of how low-oxygen stress responses are initiated by oleoyl-CoA in plants provide useful leads for enhancing future food security.
2018-04-30 | GSE97186 | GEO
Project description:Study on gene expression in multifunctional protein 2 deficient mice. Liver samples of two days old mice in normal conditions are used. In total 8 arrays were hybridized corresponding to 4 KO mice and 4 WT mice Results: Cholesterol synthesis is induced and ppar alpha targets also differentially expressed between KO and WT. Keywords: Knockout gene expression study; genetic modification
2008-11-06 | GSE10895 | GEO
Project description:Pre-pubertal (21 days old) WT or ERa knockout we compared RNA from 21-day old WT and Ex3aERKO uteri that were treated with saline vehicle (V) estradiol (E2) or IGF1 for 2 hours or 24 hours
2020-04-29 | GSE148006 | GEO
Project description:DNA G-quadruplex structure participates in regulation of lipid metabolism through Acyl-CoA binding protein
| PRJNA833674 | ENA