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.
Study ID | ST003378 |
Study Title | Effects of Aldehydes on lipid metabolism in mice |
Study 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 | Feinstein Institutes for Medical Research |
Last Name | Lopa |
First Name | Mishra |
Address | 350 Community Drive, Mahasset, NY, 11030 |
lopamishra2@gmail.com | |
Phone | 516-562-1307 |
Submit Date | 2024-07-31 |
Raw Data Available | Yes |
Raw Data File Type(s) | cdf |
Analysis Type Detail | LC-MS |
Release Date | 2024-08-06 |
Release Version | 1 |
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 |
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 |
---|---|---|---|
SA367206 | S53 | Aldh2-knockout | Liver |
SA367207 | S7 | Aldh2-knockout | Liver |
SA367208 | S67 | Aldh2-knockout | Liver |
SA367209 | S70 | Aldh2-knockout | Liver |
SA367210 | S75 | Aldh2-knockout | Liver |
SA367211 | S76 | Aldh2-knockout | Liver |
SA367212 | S4 | Aldh2-knockout | Liver |
SA367213 | S74 | Aldh2-knockout | Liver |
SA367214 | S11 | Aldh2-knockout | Liver |
SA367215 | S55 | Aldh2-knockout | Liver |
SA367216 | S46 | Aldh2-knockout | Liver |
SA367217 | S28 | Aldh2-knockout | Liver |
SA367218 | S32 | Aldh2-knockout | Liver |
SA367219 | S33 | Aldh2-knockout | Liver |
SA367220 | S34 | Aldh2-knockout | Liver |
SA367221 | S25 | Aldh2-knockout | Liver |
SA367222 | S54 | Aldh2-knockout | Liver |
SA367223 | S13 | Aldh2-knockout | Liver |
SA367224 | S49 | Aldh2-knockout | Liver |
SA367225 | S12 | Aldh2-knockout | Liver |
SA367186 | S58 | Aldh2-/-Sptbn1+/- | Liver |
SA367187 | S37 | Aldh2-/-Sptbn1+/- | Liver |
SA367188 | S10 | Aldh2-/-Sptbn1+/- | Liver |
SA367189 | S6 | Aldh2-/-Sptbn1+/- | Liver |
SA367190 | S73 | Aldh2-/-Sptbn1+/- | Liver |
SA367191 | S16 | Aldh2-/-Sptbn1+/- | Liver |
SA367192 | S27 | Aldh2-/-Sptbn1+/- | Liver |
SA367193 | S39 | Aldh2-/-Sptbn1+/- | Liver |
SA367194 | S38 | Aldh2-/-Sptbn1+/- | Liver |
SA367195 | S60 | Aldh2-/-Sptbn1+/- | Liver |
SA367196 | S48 | Aldh2-/-Sptbn1+/- | Liver |
SA367197 | S17 | Aldh2-/-Sptbn1+/- | Liver |
SA367198 | S59 | Aldh2-/-Sptbn1+/- | Liver |
SA367199 | S79 | Aldh2-/-Sptbn1+/- | Liver |
SA367200 | S80 | Aldh2-/-Sptbn1+/- | Liver |
SA367201 | S31 | Aldh2-/-Sptbn1+/- | Liver |
SA367202 | S81 | Aldh2-/-Sptbn1+/- | Liver |
SA367203 | S18 | Aldh2-/-Sptbn1+/- | Liver |
SA367204 | S52 | Aldh2-/-Sptbn1+/- | Liver |
SA367205 | S69 | Aldh2-/-Sptbn1+/- | Liver |
SA367162 | S56 | - | - |
SA367163 | S29 | - | - |
SA367164 | S35 | - | - |
SA367165 | S41 | - | - |
SA367166 | S42 | - | - |
SA367167 | S2 | - | - |
SA367168 | S44 | - | - |
SA367169 | S50 | - | - |
SA367170 | S62 | - | - |
SA367171 | S22 | - | - |
SA367172 | S63 | - | - |
SA367173 | S64 | - | - |
SA367174 | S65 | - | - |
SA367175 | S71 | - | - |
SA367176 | S77 | - | - |
SA367177 | S83 | - | - |
SA367178 | S84 | - | - |
SA367179 | S23 | - | - |
SA367180 | S1 | - | - |
SA367181 | S21 | - | - |
SA367182 | S14 | - | - |
SA367183 | S8 | - | - |
SA367184 | S20 | - | - |
SA367185 | S43 | - | - |
SA367226 | S19 | Wild-type | Liver |
SA367227 | S3 | Wild-type | Liver |
SA367228 | S57 | Wild-type | Liver |
SA367229 | S82 | Wild-type | Liver |
SA367230 | S30 | Wild-type | Liver |
SA367231 | S24 | Wild-type | Liver |
SA367232 | S51 | Wild-type | Liver |
SA367233 | S78 | Wild-type | Liver |
SA367234 | S5 | Wild-type | Liver |
SA367235 | S36 | Wild-type | Liver |
SA367236 | S47 | Wild-type | Liver |
SA367237 | S40 | Wild-type | Liver |
SA367238 | S15 | Wild-type | Liver |
SA367239 | S72 | Wild-type | Liver |
SA367240 | S61 | Wild-type | Liver |
SA367241 | S45 | Wild-type | Liver |
SA367242 | S68 | Wild-type | Liver |
SA367243 | S9 | Wild-type | Liver |
SA367244 | S66 | Wild-type | Liver |
SA367245 | S26 | Wild-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 | QTOF | QTOF | QTOF | QTOF |
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: | QTOF |
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: | QTOF |
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: | QTOF |
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: | QTOF |
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 |