Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of dietary serine/glycine restriction and myriocin treatment on hepatic sphingolipid diversity during prolonged high fat diet feeding.

ABSTRACT: We wanted to determine the impact of dietary serine/glycine restriction on hepatic sphingolipidome.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Liver

SUBMITTER: Michal Handzlik

PROVIDER: ST002344 | MetabolomicsWorkbench | Fri Nov 11 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

The impact of myriocin and dietary serine restriction on paw skin sphingolipid diversity

Project description:We analyzed paw skin polar and lipid metabolites in mice (C57BL/6J) in response to two dietary interventions. The first was: 1) low fat (LFD), 2) serine/glycine-free LFD (-SG LFD), high fat (HFD), and serine/glycine-free HFD (-SG HFD). And the second was: 1) low fat (LFD), high fat (HFD), serine/glycine-free HFD (-SG HFD), and serine/glycine-free HFD (-SG HFD) with myriocin (0.3 mg/kg every other day) treatment. The goal of the study was to determine the impact of dietary serine/glycine restriction and myriocin treatment on the hepatic lipidome.

2022-11-11 | ST002343 | MetabolomicsWorkbench

Myriocin rescue of serine-associated hepatic lipid diversity

Project description:We analyzed hepatic polar and lipid metabolites in mice (C57BL/6J) in response to two dietary interventions. The first was: 1) low fat (LFD), 2) serine/glycine-free LFD (-SG LFD), high fat (HFD), and serine/glycine-free HFD (-SG HFD). And the second was: 1) low fat (LFD), high fat (HFD), serine/glycine-free HFD (-SG HFD), and serine/glycine-free HFD (-SG HFD) with myriocin (0.3 mg/kg every other day) treatment. The goal of the study was to determine the impact of dietary serine/glycine restriction and myriocin treatment on the hepatic lipidome.

2022-11-10 | ST002339 | MetabolomicsWorkbench

Serine restriction alters sphingolipid diversity to constrain tumour growth.

Project description:Serine, glycine and other nonessential amino acids are critical for tumour progression, and strategies to limit their availability are emerging as potential therapies for cancer1-3. However, the molecular mechanisms driving this response remain unclear and the effects on lipid metabolism are relatively unexplored. Serine palmitoyltransferase (SPT) catalyses the de novo biosynthesis of sphingolipids but also produces noncanonical 1-deoxysphingolipids when using alanine as a substrate4,5. Deoxysphingolipids accumulate in the context of mutations in SPTLC1 or SPTLC26,7-or in conditions of low serine availability8,9-to drive neuropathy, and deoxysphinganine has previously been investigated as an anti-cancer agent10. Here we exploit amino acid metabolism and the promiscuity of SPT to modulate the endogenous synthesis of toxic deoxysphingolipids and slow tumour progression. Anchorage-independent growth reprogrammes a metabolic network involving serine, alanine and pyruvate that drives the endogenous synthesis and accumulation of deoxysphingolipids. Targeting the mitochondrial pyruvate carrier promotes alanine oxidation to mitigate deoxysphingolipid synthesis and improve spheroid growth, similar to phenotypes observed with the direct inhibition of SPT or ceramide synthesis. Restriction of dietary serine and glycine potently induces the accumulation of deoxysphingolipids while decreasing tumour growth in xenograft models in mice. Pharmacological inhibition of SPT rescues xenograft growth in mice fed diets restricted in serine and glycine, and the reduction of circulating serine by inhibition of phosphoglycerate dehydrogenase (PHGDH) leads to the accumulation of deoxysphingolipids and mitigates tumour growth. The promiscuity of SPT therefore links serine and mitochondrial alanine metabolism to membrane lipid diversity, which further sensitizes tumours to metabolic stress.

| S-EPMC7606299 | biostudies-literature

Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis

Project description:Here we show that suppressing the serine biosynthesis pathway, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase or by exogenous serine and glycine restriction, robustly enhances polarization of interferon-g-activated macrophages (M(IFN-g)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo.To further explore its mechanism, we used high-throughput sequencing technology (RNA-seq) to assess gene expression in serine-deficiency or not BMDMs

2022-02-19 | GSE196840 | GEO

Serine supplementation and hepatic and skin sphingolipid diversity

Project description:We analyzed hepatic and paw skin lipid metabolites in mice (BKS-db/db) in response to dietary serine supplementation.

2022-11-11 | ST002340 | MetabolomicsWorkbench

Hotspot mutations induce metabolic reprogramming and vulnerability to serine deprivation

Project description:Cancer-associated mutations in the spliceosome gene create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are not well understood. Here we provide evidence that aberrant splicing by mutant alters the transcriptome, proteome, and metabolome of human cells, leading to missplicing-associated downregulation of metabolic genes, decreased mitochondrial respiration, and suppression of the serine synthesis pathway. We also find that mutant induces vulnerability to deprivation of the nonessential amino acid serine, which is mediated by missplicing-associated downregulation of the serine synthesis pathway enzyme PHGDH. This vulnerability is manifest both in vitro and in vivo, as dietary restriction of serine and glycine in mice is able to inhibit the growth ofMUT xenografts. These findings describe a novel role for mutations in altered energy metabolism, and they offer a new therapeutic strategy againstMUT cancers.

2019-12-31 | GSE134475 | GEO

Expression data of peritoneal macrophages from Wild-type mouse cultured in control or serine/glycine-depleted medium.

Project description:Activation of signaling pathways downstream of Toll-like receptor 4 upregulate expression of genes related to serine metabolism. We cultured peritoneal macrophages in control or serine/glycine-depleted medium for 24 hr, stimulated them with LPS (10 ng/ml) for 6 or 12 hr, and collected them to compare the gene expression. Microarray analysis revealed that serine/glycine-depletion in peritoneal macrophages upregulates gene expression of enzymes for serine biosynthesis.

2021-03-31 | GSE156325 | GEO

Exogenous and endogenous serine modulate polarization of tumor-associated macrophages to influence development of nasopharyngeal carcinoma

Project description:To investigate the global gene expression pattern in response to removal of exogenous serine/glycine from the medium, RNA-seq was performed using C666-1 cells cultured in CM or -SG medium for 24 h. The volcano plot exhibited 60 up-regulated and 123 down-regulated genes in C666-1 cells subjected to exogenous serine/glycine deprivation.

2024-04-09 | GSE263382 | GEO

Expression data from brain tissue of Rattus norvegicus treated with D-Serine

Project description:d-serine is naturally present throughout the human body. It is also used as add-on therapy for treatment-refractory schizophrenia. d-Serine interacts with the strychnine-insensitive glycine binding site of NMDA receptor, and this interaction could lead to potentially toxic activity (i.e., excitotoxicity) in brain tissue. The transcriptomic changes that occur in the brain after d-serine exposure have not been fully explored. Affymetrix microarray technology was used to determine differential gene expression resulting from D-Serine exposure. Keywords: Dose course Male Fisher 344 rats aged 11-12 weeks were treated with various doses (0, 5, 20, 50, 200 and 500 mg/kg) of d-serine and terminally sacrificed 96 hours post-exposure. An approximate 30mg-section of the forebrain was processed for total RNA isolation.

2008-03-08 | E-GEOD-10748 | biostudies-arrayexpress

Simultaneous perturbation of multiple metabolic pathways by non-essential amino acid restriction is a potent cancer radio-sensitisation strategy

Project description:Cellular metabolism is an integral component of cellular adaptation to stress, consequently, metabolism plays a pivotal role in the resistance of cancer cells to a range of treatment modalities. Radiotherapy is used to treat approximately half of all cancer patients, however, most are either inherently radioresistant or acquire resistance over time. Effective radiotherapy relies on generating an overwhelming burden of DNA damage which triggers cell death. In response to radiotherapy cancer cells engage antioxidant and DNA repair mechanisms which mitigate and remove DNA damage, facilitating cancer cell survival. Given the reliance of these resistance mechanisms on amino acid metabolism we hypothesised that controlling the availability of the exogenous amino acids serine and glycine would be an effective strategy to radiosensitive cancer cells. Here we show that serine and glycine restriction sensitised a range of cancer cell lines, patient derived organoids and syngeneic mouse tumour models to radiotherapy. Comprehensive metabolomic analysis of central carbon metabolism revealed that amino acid restriction impacted not only glutathione and nucleotide synthesis but had an unexpected impact on the TCA cycle and antagonised a key cellular redox response to radiotherapy mediated by reductive carboxylation.

2022-11-02 | GSE190668 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data