Summary of Study ST003127

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 PR001944. The data can be accessed directly via it's Project DOI: 10.21228/M8FD9G This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST003127
Study TitleEffect of high fat diet on heart lipidome in CHCHD10 mutant mice
Study SummaryMutations in CHCHD10, a mitochondrial protein with undefined functions, are associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L) develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts, mtISR is accompanied by a metabolic rewiring characterized by increased reliance on glycolysis rather than fatty acid oxidation. To counteract this metabolic rewiring, heterozygous S55L mice were subjected to chronic high fat diet (HFD) to decrease insulin sensitivity and glucose uptake and enhance fatty acid utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant hearts and significantly extended the survival of mutant female mice affected by severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that HFD increased fatty acid utilization and ameliorated cardiomyopathy markers. Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L heart, suggesting activation of quality control mechanisms. Overall, our findings indicate that metabolic therapy can be effective in mitochondrial cardiomyopathies associated with proteotoxic stress.
Institute
Weill Cornell Medicine
Last NameSouthwell
First NameNneka
Address407 E 61st St
Emailnns4001@med.cornell.edu
Phone646-962-8172
Submit Date2024-03-06
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-03-26
Release Version1
Nneka Southwell Nneka Southwell
https://dx.doi.org/10.21228/M8FD9G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005126 AN005127
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Imtakt Cadenza CD-C18 (150 x 2.1mm, 3um) Imtakt Cadenza CD-C18 (150 x 2.1mm, 3um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Peak Intensity Peak Intensity

MS:

MS ID:MS004862
Analysis ID:AN005126
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:A data-dependent mass spectrometric acquisition method was used for lipid identification. In this method, each MS survey scan was followed by up to 10 MS/MS scans performed on the most abundant ions. Data was acquired in positive and negative mode in separate runs. The following electrospray parameters were used: spray voltage 3.0 kV, heated capillary temperature 350 °C, HESI probe temperature 350 °C, sheath gas, 35 units; auxiliary gas 10 units. For MS scans: resolution, 70,000 (at m/z 200); automatic gain control target, 3e6; maximum injection time, 200 ms; scan range, 250-1800 m/z. For MS/MS scans: resolution, 17,500 (at 200 m/z); automatic gain control target, 1e5 ions; maximum injection time, 75 ms; isolation window, 1 m/z; NCE, stepped 20,30 and 40. The LC-MS results were processed using MS-DIAL software (version 4.9) for lipid identification and relative quantitation.
Ion Mode:POSITIVE
Analysis Protocol File:Method_Lipidomics.pdf
  
MS ID:MS004863
Analysis ID:AN005127
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:A data-dependent mass spectrometric acquisition method was used for lipid identification. In this method, each MS survey scan was followed by up to 10 MS/MS scans performed on the most abundant ions. Data was acquired in positive and negative mode in separate runs. The following electrospray parameters were used: spray voltage 3.0 kV, heated capillary temperature 350 °C, HESI probe temperature 350 °C, sheath gas, 35 units; auxiliary gas 10 units. For MS scans: resolution, 70,000 (at m/z 200); automatic gain control target, 3e6; maximum injection time, 200 ms; scan range, 250-1800 m/z. For MS/MS scans: resolution, 17,500 (at 200 m/z); automatic gain control target, 1e5 ions; maximum injection time, 75 ms; isolation window, 1 m/z; NCE, stepped 20,30 and 40. The LC-MS results were processed using MS-DIAL software (version 4.9) for lipid identification and relative quantitation.
Ion Mode:NEGATIVE
Analysis Protocol File:Method_Lipidomics.pdf
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