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
Email	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

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Sample Preparation:

Sampleprep ID:	SP003252
Sampleprep Summary:	Untargeted and targeted metabolomics: Serum metabolites were extracted with 80% methanol. The extracts were clarified by centrifugation at 15,000 g for 10 min. The supernatant was collected and dried down using a SpeedVac. For lipidomics analyses: 180 µl of 90% isopropanol was added to 20 µl serum. 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. Free Fatty Acids: Free fatty acids were extracted from serum using 90% methanol (LC/MS grade, Thermo Scientific). The extracts were clarified by centrifugation at 15,000 g for 10 min. The supernatant was collected and dried down using a SpeedVac. The dried sample was reconstituted using 50% methanol prior to LC-MS analysis.

Sampleprep ID:

SP003252

Sampleprep Summary:

Untargeted and targeted metabolomics: Serum metabolites were extracted with 80% methanol. The extracts were clarified by centrifugation at 15,000 g for 10 min. The supernatant was collected and dried down using a SpeedVac. For lipidomics analyses: 180 µl of 90% isopropanol was added to 20 µl serum. 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. Free Fatty Acids: Free fatty acids were extracted from serum using 90% methanol (LC/MS grade, Thermo Scientific). The extracts were clarified by centrifugation at 15,000 g for 10 min. The supernatant was collected and dried down using a SpeedVac. The dried sample was reconstituted using 50% methanol prior to LC-MS analysis.