Summary of project PR001944
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
| 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 |
Summary of all studies in project PR001944
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003126 | Effect of high fat diet on heart metabolome of CHCHD10 mutant mice | Mus musculus | Weill Cornell Medicine | MS* | 2024-03-26 | 1 | 40 | Uploaded data (1.1G)* |
| ST003127 | Effect of high fat diet on heart lipidome in CHCHD10 mutant mice | Mus musculus | Weill Cornell Medicine | MS | 2024-03-26 | 1 | 40 | Uploaded data (1.3G)* |
| ST003128 | Effect of high fat diet on serum fatty acids, lipidome and metabolome in CHCHD10 mutant mice | Mus musculus | Weill Cornell Medicine | MS* | 2024-03-26 | 1 | 72 | Uploaded data (2.8G)* |
