Summary of Study ST003126
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 | ST003126 |
| Study Title | Effect of high fat diet on heart metabolome of 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 | 2024-03-03 |
| 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 | AN005125 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Vanquish |
| Column | Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap |
| Ion Mode | UNSPECIFIED |
| Units | Peak Intensity |
MS:
| MS ID: | MS004861 |
| Analysis ID: | AN005125 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The MS data was processed using XCalibur 4.1 (Thermo Scientific) to obtain the metabolite signal intensity for relative quantitation. Targeted identification was available for 205 metabolites based on an in-house library established using known chemical standards. Identification required exact mass (within 5ppm) and standard retention times. For untargeted metabolomics, metabolites were identified by mass matching of the MS signal to metabolites in the HMDB database. If multiple metabolites in the database were matched to a certain MS signal, all matched metabolites were grouped into a single identification, and ordered based on the number of references included in the HMDB database (high to low). We used the first ranked metabolite in the downstream analyses. When multiple values with the same metabolite attribution occurred (different metabolites with same mass and retention time), we opted to use all values in the analyses to avoid biases on which intensities/attributions to consider. Peak intensities for metabolites were screened for missing values and relative metabolite abundance data was analyzed by using MetaboAnalyst software version 5.0 (Pang et al, 2021). Metabolite significance was determined with one-way ANOVA with post-hoc t-tests, with the cutoff being a raw p value < 0.05, and the pathway significance cutoff was FDR corrected p value < 0.05. |
| Ion Mode: | UNSPECIFIED |
| Analysis Protocol File: | Protocol_HeartMetabolomics.pdf |
