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.
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 | ST003127 |
| Study Title | Effect of high fat diet on heart lipidome 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:
Project:
| Project ID: | PR001944 |
| Project DOI: | doi: 10.21228/M8FD9G |
| Project Title: | High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice |
| Project 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 |
| Email: | nns4001@med.cornell.edu |
| Phone: | 646-962-8172 |
Subject:
| Subject ID: | SU003244 |
| 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 | Sample source | Genotype | Treatment | Sex | Age |
|---|---|---|---|---|---|---|
| SA338927 | HL_HetCD_1 | Heart | CHCHD10 S55L Het | Control Diet | F | 75 |
| SA338928 | HL_HetCD_2 | Heart | CHCHD10 S55L Het | Control Diet | F | 75 |
| SA338929 | HL_HetCD_5 | Heart | CHCHD10 S55L Het | Control Diet | F | 75 |
| SA338930 | HL_HetCD_3 | Heart | CHCHD10 S55L Het | Control Diet | F | 75 |
| SA338931 | HL_HetCD_10 | Heart | CHCHD10 S55L Het | Control Diet | M | 75 |
| SA338932 | HL_HetCD_7 | Heart | CHCHD10 S55L Het | Control Diet | M | 75 |
| SA338933 | HL_HetCD_8 | Heart | CHCHD10 S55L Het | Control Diet | M | 75 |
| SA338934 | HL_HetCD_6 | Heart | CHCHD10 S55L Het | Control Diet | M | 75 |
| SA338935 | HetCD_mixneg | Heart | CHCHD10 S55L Het | Control Diet | N/A | 75 |
| SA338936 | HetCD_mixpos | Heart | CHCHD10 S55L Het | Control Diet | N/A | 75 |
| SA338937 | HL_HetHFD_2 | Heart | CHCHD10 S55L Het | High Fat Diet | F | 75 |
| SA338938 | HL_HetHFD_3 | Heart | CHCHD10 S55L Het | High Fat Diet | F | 75 |
| SA338939 | HL_HetHFD_5 | Heart | CHCHD10 S55L Het | High Fat Diet | F | 75 |
| SA338940 | HL_HetHFD_4 | Heart | CHCHD10 S55L Het | High Fat Diet | F | 75 |
| SA338941 | HL_HetHFD_9 | Heart | CHCHD10 S55L Het | High Fat Diet | M | 75 |
| SA338942 | HL_HetHFD_7 | Heart | CHCHD10 S55L Het | High Fat Diet | M | 75 |
| SA338943 | HL_HetHFD_10 | Heart | CHCHD10 S55L Het | High Fat Diet | M | 75 |
| SA338944 | HL_HetHFD_6 | Heart | CHCHD10 S55L Het | High Fat Diet | M | 75 |
| SA338945 | HetHFD_mixpos | Heart | CHCHD10 S55L Het | High Fat Diet | N/A | 75 |
| SA338946 | HetHFD_mixneg | Heart | CHCHD10 S55L Het | High Fat Diet | N/A | 75 |
| SA338947 | HL_WTCD_1 | Heart | WT | Control Diet | F | 75 |
| SA338948 | HL_WTCD_3 | Heart | WT | Control Diet | F | 75 |
| SA338949 | HL_WTCD_2 | Heart | WT | Control Diet | F | 75 |
| SA338950 | HL_WTCD_4 | Heart | WT | Control Diet | F | 75 |
| SA338951 | HL_WTCD_10 | Heart | WT | Control Diet | M | 75 |
| SA338952 | HL_WTCD_6 | Heart | WT | Control Diet | M | 75 |
| SA338953 | HL_WTCD_8 | Heart | WT | Control Diet | M | 75 |
| SA338954 | HL_WTCD_9 | Heart | WT | Control Diet | M | 75 |
| SA338955 | WTCD_mixpos | Heart | WT | Control Diet | N/A | 75 |
| SA338956 | WTCD_mixneg | Heart | WT | Control Diet | N/A | 75 |
| SA338957 | HL_WTHFD_4 | Heart | WT | High Fat Diet | F | 75 |
| SA338958 | HL_WTHFD_1 | Heart | WT | High Fat Diet | F | 75 |
| SA338959 | HL_WTHFD_3 | Heart | WT | High Fat Diet | F | 75 |
| SA338960 | HL_WTHFD_5 | Heart | WT | High Fat Diet | F | 75 |
| SA338961 | HL_WTHFD_7 | Heart | WT | High Fat Diet | M | 75 |
| SA338962 | HL_WTHFD_10 | Heart | WT | High Fat Diet | M | 75 |
| SA338963 | HL_WTHFD_8 | Heart | WT | High Fat Diet | M | 75 |
| SA338964 | HL_WTHFD_6 | Heart | WT | High Fat Diet | M | 75 |
| SA338965 | WTHFD_mixneg | Heart | WT | High Fat Diet | N/A | 75 |
| SA338966 | WTHFD_mixpos | Heart | WT | High Fat Diet | N/A | 75 |
| Showing results 1 to 40 of 40 |
Collection:
| Collection ID: | CO003237 |
| Collection Summary: | Murine heart tissue was excised and snap frozen in liquid N2. |
| Sample Type: | Heart |
Treatment:
| Treatment ID: | TR003253 |
| Treatment Summary: | CHCHD10 WT and CHCHD10 S55L heterozygous mice were treated with either a control diet (70% Carbohydrate, 20% Protein, 10% Fat) or High Fat Diet (60% Fat, 20% Protein, 20% Carbohydrate) in utero until 75 days of age. |
Sample Preparation:
| Sampleprep ID: | SP003251 |
| Sampleprep Summary: | In brief, 1 ml of 90% isopropanol was added to 15 mg of homogenized heart tissue. Samples were vortexed for 2 min, sonicated for 1 min using a probe sonicator and centrifuged at 15,000 g for 10 min. The supernatant was collected and dried down using a SpeedVac. The dried samples were reconstituted using acetonitrile/isopropanol/water 65:30:5 containing stable isotope labeled internal lipid standards (Splash Lipidomix, Avanti Polar Lipids) prior to LC-MS analysis. |
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 |
Chromatography:
| Chromatography ID: | CH003879 |
| Methods Filename: | Method_Lipidomics.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Imtakt Cadenza CD-C18 (150 x 2.1mm, 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 |
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 |
