Summary of Study ST003128
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.
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 | ST003128 |
| Study Title | Effect of high fat diet on serum fatty acids, lipidome and metabolome in CHCHD10 mutant mice |
| Study Summary | Mutations 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 Name | Southwell |
| First Name | Nneka |
| Address | 407 E 61st St |
| nns4001@med.cornell.edu | |
| Phone | 646-962-8172 |
| Submit Date | 2024-03-06 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-03-26 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005128 | AN005129 | AN005130 |
|---|---|---|---|
| Analysis type | MS | MS | MS |
| Chromatography type | HILIC | Reversed phase | Reversed phase |
| Chromatography system | Thermo Vanquish | Thermo Vanquish | Thermo Vanquish |
| Column | SeQuant ZIC-pHILIC (150 x 2.1mm, 5um) | Imtakt Cadenza CD-C18 (150 x 2.1 mm, 3um) | Imtakt Cadenza CD-C18 (150 x 2.1 mm, 3um) |
| MS Type | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | UNSPECIFIED | NEGATIVE | POSITIVE |
| Units | Peak Intensity | Peak Intensity | Peak Intensity |
Chromatography:
| Chromatography ID: | CH003880 |
| Chromatography Summary: | Serum targeted and untargeted metabolomics |
| Methods Filename: | Serum_MS_and_Data_Analysis.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | SeQuant ZIC-pHILIC (150 x 2.1mm, 5um) |
| Column Temperature: | 35 |
| Flow Gradient: | 85% to 30% A in 20 min followed by a wash with 30% A and re-equilibration at 85% A |
| Flow Rate: | 150 µl/min |
| Solvent A: | 100% acetonitrile |
| Solvent B: | 100% water; 0.1% ammonium hydroxide; 20 mM ammonium acetate |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH003881 |
| Chromatography Summary: | Serum free fatty acids |
| Methods Filename: | Serum_MS_and_Data_Analysis.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Imtakt Cadenza CD-C18 (150 x 2.1 mm, 3um) |
| Column Temperature: | 35 |
| Flow Gradient: | 0–1.5 min, 50% B; 1.5-3 min, 50-90% B; 3-5.5 min, 90-95% B; 5.5-10 min, 95% B, followed by 5 min of re-equilibration |
| Flow Rate: | 150 µl/min |
| Solvent A: | 100% water; 5 mM ammonium acetate |
| Solvent B: | 85% isopropanol/10% acetonitrile/5% water; 5 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003882 |
| Chromatography Summary: | Serum lipidomics |
| Methods Filename: | Serum_MS_and_Data_Analysis.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Imtakt Cadenza CD-C18 (150 x 2.1 mm, 3um) |
| Column Temperature: | 35 |
| Flow Gradient: | 0–1.5 min, 32% B; 1.5-4 min, 32-45% B; 4-5 min, 45-52% B; 5-8 min, 52-58% B; 8-11 min, 58-66% B; 11-14 min, 66-70% B; 14-18 min, 70-75% B; 21-25 min, isocratic 97% B, 25-25.1 min 97-32% B |
| Flow Rate: | 200 µl/min |
| Solvent A: | 60% acetonitrile/40% water; 10 mM ammonium formate; 0.1% formic acid |
| Solvent B: | 90% isopropanol/10% acetonitrile; 10 mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
