Summary of Study ST003378

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002095. The data can be accessed directly via it's Project DOI: 10.21228/M8TC1H This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST003378
Study TitleEffects of Aldehydes on lipid metabolism in mice
Study SummaryObesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD and MASH) affect over a third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2-/- and Aldh2-/-Sptbn1+/- mice develop phenotypes of human Metabolic Syndrome (MetS) and MASH with a striking accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). While phospholipids are often modified by reactive aldehydes that accumulate in the absence of ALDH2, to understand the mechanisms for the differences in liver metabolism in ASKO mice, we analyzed liver metabolomics and lipidomics from mice models. Briefly, C57BL/6 mice (n=15) were from 3 groups (WT, Aldh2-/-(ko), Aldh2-/-Sptbn1+/-(double), n=5 per group) and fed normal chow diet for 10 months. For quality control, 6 QC samples were also included in the analysis (total 21 samples). We observed that livers of Aldh2-/-Sptbn1+/- mice had substantially higher levels of all investigated phospholipids, including ≥ 2-fold increase in 26% of phosphatidylethanolamine (PE) lipid types and ≥ 2-fold increase in 32% of phosphatidylserine (PS) lipid types, compared to livers of WT mice. Similarly, increased abundances of TGs and diacylglycerides (DGs) lipid types were also observed in the livers of Aldh2-/-Sptbn1+/- mice. These results demonstrated that Aldehydes altered lipid metabolism which may be implicated in the progression of liver MetS, MASLD/MASH in Aldh2-/-Sptbn1+/- mice.
Institute
Feinstein Institutes for Medical Research
Last NameLopa
First NameMishra
Address350 Community Drive, Mahasset, NY, 11030
Emaillopamishra2@gmail.com
Phone516-562-1307
Submit Date2024-07-31
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailLC-MS
Release Date2024-08-06
Release Version1
Mishra Lopa Mishra Lopa
https://dx.doi.org/10.21228/M8TC1H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002095
Project DOI:doi: 10.21228/M8TC1H
Project Title:Effects of Aldehydes on lipid metabolism in mice
Project Summary:Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD and MASH) affect over a third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2-/- and Aldh2-/-Sptbn1+/- mice develop phenotypes of human Metabolic Syndrome (MetS) and MASH with a striking accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). While phospholipids are often modified by reactive aldehydes that accumulate in the absence of ALDH2, to understand the mechanisms for the differences in liver metabolism in ASKO mice, we analyzed liver metabolomics and lipidomics from mice models. Briefly, C57BL/6 mice (n=15) were from 3 groups (WT, Aldh2-/-(ko), Aldh2-/-Sptbn1+/-(double), n=5 per group) and fed normal chow diet for 10 months. For quality control, 6 QC samples were also included in the analysis (total 21 samples). We observed that livers of Aldh2-/-Sptbn1+/- mice had substantially higher levels of all investigated phospholipids, including ≥ 2-fold increase in 26% of phosphatidylethanolamine (PE) lipid types and ≥ 2-fold increase in 32% of phosphatidylserine (PS) lipid types, compared to livers of WT mice. Similarly, increased abundances of TGs and diacylglycerides (DGs) lipid types were also observed in the livers of Aldh2-/-Sptbn1+/- mice. These results demonstrated that Aldehydes altered lipid metabolism which may be implicated in the progression of liver MetS, MASLD/MASH in Aldh2-/-Sptbn1+/- mice.
Institute:Northwell health
Last Name:Mishra
First Name:Lopa
Address:350 Community Drive, Manhasset, NY, 11030, USA
Email:lopamishra2@gmail.com
Phone:516-562-1307
Publications:https://pubmed.ncbi.nlm.nih.gov/39217614, doi: 10.1016/j.celrep.2024.114676

Subject:

Subject ID:SU003499
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Sample source
SA367206S53Aldh2-knockout Liver
SA367207S7Aldh2-knockout Liver
SA367208S67Aldh2-knockout Liver
SA367209S70Aldh2-knockout Liver
SA367210S75Aldh2-knockout Liver
SA367211S76Aldh2-knockout Liver
SA367212S4Aldh2-knockout Liver
SA367213S74Aldh2-knockout Liver
SA367214S11Aldh2-knockout Liver
SA367215S55Aldh2-knockout Liver
SA367216S46Aldh2-knockout Liver
SA367217S28Aldh2-knockout Liver
SA367218S32Aldh2-knockout Liver
SA367219S33Aldh2-knockout Liver
SA367220S34Aldh2-knockout Liver
SA367221S25Aldh2-knockout Liver
SA367222S54Aldh2-knockout Liver
SA367223S13Aldh2-knockout Liver
SA367224S49Aldh2-knockout Liver
SA367225S12Aldh2-knockout Liver
SA367186S58Aldh2-/-Sptbn1+/- Liver
SA367187S37Aldh2-/-Sptbn1+/- Liver
SA367188S10Aldh2-/-Sptbn1+/- Liver
SA367189S6Aldh2-/-Sptbn1+/- Liver
SA367190S73Aldh2-/-Sptbn1+/- Liver
SA367191S16Aldh2-/-Sptbn1+/- Liver
SA367192S27Aldh2-/-Sptbn1+/- Liver
SA367193S39Aldh2-/-Sptbn1+/- Liver
SA367194S38Aldh2-/-Sptbn1+/- Liver
SA367195S60Aldh2-/-Sptbn1+/- Liver
SA367196S48Aldh2-/-Sptbn1+/- Liver
SA367197S17Aldh2-/-Sptbn1+/- Liver
SA367198S59Aldh2-/-Sptbn1+/- Liver
SA367199S79Aldh2-/-Sptbn1+/- Liver
SA367200S80Aldh2-/-Sptbn1+/- Liver
SA367201S31Aldh2-/-Sptbn1+/- Liver
SA367202S81Aldh2-/-Sptbn1+/- Liver
SA367203S18Aldh2-/-Sptbn1+/- Liver
SA367204S52Aldh2-/-Sptbn1+/- Liver
SA367205S69Aldh2-/-Sptbn1+/- Liver
SA367162S56- -
SA367163S29- -
SA367164S35- -
SA367165S41- -
SA367166S42- -
SA367167S2- -
SA367168S44- -
SA367169S50- -
SA367170S62- -
SA367171S22- -
SA367172S63- -
SA367173S64- -
SA367174S65- -
SA367175S71- -
SA367176S77- -
SA367177S83- -
SA367178S84- -
SA367179S23- -
SA367180S1- -
SA367181S21- -
SA367182S14- -
SA367183S8- -
SA367184S20- -
SA367185S43- -
SA367226S19Wild-type Liver
SA367227S3Wild-type Liver
SA367228S57Wild-type Liver
SA367229S82Wild-type Liver
SA367230S30Wild-type Liver
SA367231S24Wild-type Liver
SA367232S51Wild-type Liver
SA367233S78Wild-type Liver
SA367234S5Wild-type Liver
SA367235S36Wild-type Liver
SA367236S47Wild-type Liver
SA367237S40Wild-type Liver
SA367238S15Wild-type Liver
SA367239S72Wild-type Liver
SA367240S61Wild-type Liver
SA367241S45Wild-type Liver
SA367242S68Wild-type Liver
SA367243S9Wild-type Liver
SA367244S66Wild-type Liver
SA367245S26Wild-type Liver
Showing results 1 to 84 of 84

Collection:

Collection ID:CO003492
Collection Summary:C57BL/6 mice (n=15) were from 3 groups (WT, Aldh2-/-(ko), Aldh2-/-Sptbn1+/-(double), n=5 per group) and fed normal chow diet for 10 months. Mice were euthanized and biospecimens were collected at the study endpoints. For quality control, 6 QC samples were also included in the analysis (total 21 samples).
Sample Type:Liver

Treatment:

Treatment ID:TR003508
Treatment Summary:No treatment. Mice from different genotypes (WT, Aldh2-/-, Aldh2-/-Sptbn1+/-) were fed on normal chow diet for 10 months.

Sample Preparation:

Sampleprep ID:SP003506
Sampleprep Summary:Add 150 μL of chilled Water/Methanol/isopropyl alcohol (IPA) (35:25:40) containing the internal standards (Add 10 μL of Debrisoquine (1 mg/mL in ddH2O) and add 50 μL of 4-NBA (1 mg/mL in methanol) to 10 mL of 35% Water, 25% Methanol, 40% IPA) to the tissue (not more than 5mg of tissue). Homogenize samples on ice Add 150 ACN to the Homogenized samples. Vortex and keep it at -20 °C for 20-30 minutes. Centrifuge samples at 14000 rpm for 15 min at 4 °C. Transfer Supernatant to MS sample vial (GLASS), cap, and run. Keep pellet for protein analysis.

Combined analysis:

Analysis ID AN005530 AN005531 AN005532 AN005533
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase Reversed phase
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column ACQUITY UPLC BEH C18 (2.1 x 50mm, 1.7um) ACQUITY UPLC BEH C18 (2.1 x 50mm, 1.7um) ACQUITY UPLC CSH C18 (2.1 x 50mm, 1.7um) ACQUITY UPLC CSH C18 (2.1 x 50mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type Triple quadrupole Triple quadrupole Triple quadrupole Triple quadrupole
MS instrument name Waters Xevo TQ-S Waters Xevo TQ-S Waters Xevo TQ-S Waters Xevo TQ-S
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE
Units Normalized peak intensity Normalized peak intensity Normalized peak intensity Normalized peak intensity

Chromatography:

Chromatography ID:CH004206
Chromatography Summary:For metabolomics
Instrument Name:Waters Acquity
Column Name:ACQUITY UPLC BEH C18 (2.1 x 50mm, 1.7um)
Column Temperature:65
Flow Gradient:0-0.5 min with 95% (A)+5%(B), 0.5-8 min 2%(A)+98% (B), 8-10.5 min 2% (B)+98%(C), 10.5-11.5 min 50%(A)+50% (B), 11.5-13 min 95% (A)+5%(B)
Flow Rate:0.5 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase
Solvent C:90% isoporpanol/10% acetonitrile; 0.1% Formic Acid
  
Chromatography ID:CH004207
Chromatography Summary:For lipidomics
Instrument Name:Waters Acquity
Column Name:ACQUITY UPLC CSH C18 (2.1 x 50mm, 1.7um)
Column Temperature:65
Flow Gradient:0-0.5 min with 60% (A)+40%(B), 0.5-8.5 min 100% (B), 8.5-11 min 60% (A)+40%(B)
Flow Rate:0.5 mL/min
Solvent A:50% acetonitrile/50% water; 0.1% formic acid
Solvent B:90% isopropyl alcohol (IPA) /10% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS005255
Analysis ID:AN005530
Instrument Name:Waters Xevo TQ-S
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The column eluent was introduced directly into the mass spectrometer by electrospray. Mass spectrometry was performed on a quadrupole-time-of-flight mass spectrometer operating in either negative or positive electrospray ionization. Positive mode has a capillary voltage of 3.0 kV, a sampling cone voltage of 30 V, and a source offset of 80 V. Negative mode has a capillary voltage of 2.75 kV, a sampling cone voltage of 20 V, and a source offset of 80 V. The de-solvation gas flow was 600 L/hr. and the temperature was set to 500 ⁰C. The cone gas flow was 25 L/h, and the source temperature was 100 ⁰C. The data were acquired in the Sensitivity and MS Mode with a scan time of 0.1 seconds, and inter-scan delay at 0.08 seconds. Accurate mass was maintained by infusing Leucine Enkephalin (556.2771 m/z) in 50% aqueous acetonitrile (1.0 ng/mL ) at a rate of 10 μL/min via the lock-spray interface every 10 seconds. Data were acquired in centroid mode from 50 to 1200 m/z mass range for TOF-MS scanning. Pooled sample injections at the beginning and end of the run (one pool was created by mixing a set aliquot from all samples) were used as quality controls (QCs) to assess inconsistencies that are particularly evident in large batch acquisitions in terms of retention time drifts and variation in ion intensity over time. Peak picking from the Waters raw data was done using an R-based implementation of XCMS with parameter optimization using the Isotopologue Parameter Optimization (IPO) package. Intensity values were standardized to internal standards and protein quantification (per Bradford assay) for each sample. Data integrity check, normalization, univariate analysis and principal component analysis (PCA) was completed.
Ion Mode:POSITIVE
  
MS ID:MS005256
Analysis ID:AN005531
Instrument Name:Waters Xevo TQ-S
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The column eluent was introduced directly into the mass spectrometer by electrospray. Mass spectrometry was performed on a quadrupole-time-of-flight mass spectrometer operating in either negative or positive electrospray ionization. Positive mode has a capillary voltage of 3.0 kV, a sampling cone voltage of 30 V, and a source offset of 80 V. Negative mode has a capillary voltage of 2.75 kV, a sampling cone voltage of 20 V, and a source offset of 80 V. The de-solvation gas flow was 600 L/hr. and the temperature was set to 500 ⁰C. The cone gas flow was 25 L/h, and the source temperature was 100 ⁰C. The data were acquired in the Sensitivity and MS Mode with a scan time of 0.1 seconds, and inter-scan delay at 0.08 seconds. Accurate mass was maintained by infusing Leucine Enkephalin (556.2771 m/z) in 50% aqueous acetonitrile (1.0 ng/mL ) at a rate of 10 μL/min via the lock-spray interface every 10 seconds. Data were acquired in centroid mode from 50 to 1200 m/z mass range for TOF-MS scanning. Pooled sample injections at the beginning and end of the run (one pool was created by mixing a set aliquot from all samples) were used as quality controls (QCs) to assess inconsistencies that are particularly evident in large batch acquisitions in terms of retention time drifts and variation in ion intensity over time. Peak picking from the Waters raw data was done using an R-based implementation of XCMS with parameter optimization using the Isotopologue Parameter Optimization (IPO) package. Intensity values were standardized to internal standards and protein quantification (per Bradford assay) for each sample. Data integrity check, normalization, univariate analysis and principal component analysis (PCA) was completed.
Ion Mode:NEGATIVE
  
MS ID:MS005257
Analysis ID:AN005532
Instrument Name:Waters Xevo TQ-S
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The column eluent was introduced directly into the mass spectrometer by electrospray. Mass spectrometry was performed on a quadrupole-time-of-flight mass spectrometer operating in either negative or positive electrospray ionization. Positive mode has a capillary voltage of 3.0 kV, a sampling cone voltage of 30 V, and a source offset of 80 V. Negative mode has a capillary voltage of 2.75 kV, a sampling cone voltage of 20 V, and a source offset of 80 V. The de-solvation gas flow was 600 L/hr. and the temperature was set to 500 ⁰C. The cone gas flow was 25 L/h, and the source temperature was 100 ⁰C. The data were acquired in the Sensitivity and MS Mode with a scan time of 0.1 seconds, and inter-scan delay at 0.08 seconds. Accurate mass was maintained by infusing Leucine Enkephalin (556.2771 m/z) in 50% aqueous acetonitrile (1.0 ng/mL ) at a rate of 10 μL/min via the lock-spray interface every 10 seconds. Data were acquired in centroid mode from 50 to 1200 m/z mass range for TOF-MS scanning. Pooled sample injections at the beginning and end of the run (one pool was created by mixing a set aliquot from all samples) were used as quality controls (QCs) to assess inconsistencies that are particularly evident in large batch acquisitions in terms of retention time drifts and variation in ion intensity over time. Peak picking from the Waters raw data was done using an R-based implementation of XCMS with parameter optimization using the Isotopologue Parameter Optimization (IPO) package. Intensity values were standardized to internal standards and protein quantification (per Bradford assay) for each sample. Data integrity check, normalization, univariate analysis and principal component analysis (PCA) was completed.
Ion Mode:POSITIVE
  
MS ID:MS005258
Analysis ID:AN005533
Instrument Name:Waters Xevo TQ-S
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The column eluent was introduced directly into the mass spectrometer by electrospray. Mass spectrometry was performed on a quadrupole-time-of-flight mass spectrometer operating in either negative or positive electrospray ionization. Positive mode has a capillary voltage of 3.0 kV, a sampling cone voltage of 30 V, and a source offset of 80 V. Negative mode has a capillary voltage of 2.75 kV, a sampling cone voltage of 20 V, and a source offset of 80 V. The de-solvation gas flow was 600 L/hr. and the temperature was set to 500 ⁰C. The cone gas flow was 25 L/h, and the source temperature was 100 ⁰C. The data were acquired in the Sensitivity and MS Mode with a scan time of 0.1 seconds, and inter-scan delay at 0.08 seconds. Accurate mass was maintained by infusing Leucine Enkephalin (556.2771 m/z) in 50% aqueous acetonitrile (1.0 ng/mL ) at a rate of 10 μL/min via the lock-spray interface every 10 seconds. Data were acquired in centroid mode from 50 to 1200 m/z mass range for TOF-MS scanning. Pooled sample injections at the beginning and end of the run (one pool was created by mixing a set aliquot from all samples) were used as quality controls (QCs) to assess inconsistencies that are particularly evident in large batch acquisitions in terms of retention time drifts and variation in ion intensity over time. Peak picking from the Waters raw data was done using an R-based implementation of XCMS with parameter optimization using the Isotopologue Parameter Optimization (IPO) package. Intensity values were standardized to internal standards and protein quantification (per Bradford assay) for each sample. Data integrity check, normalization, univariate analysis and principal component analysis (PCA) was completed.
Ion Mode:NEGATIVE
  logo