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

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:	SU003245
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	Age (d)	Sex
SA338967	SL_HetCD_6	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338968	S_HetCD_2	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338969	SL_HetCD_3	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338970	SP_HetCD_1	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338971	SL_HetCD_5	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338972	SL_HetCD_2	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338973	SL_HetCD_1	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338974	SL_HetCD_4	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338975	SP_HetCD_6	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338976	S_HetCD_1	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338977	S_HetCD_5	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338978	S_HetCD_6	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338979	SP_HetCD_2	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338980	S_HetCD_4	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338981	S_HetCD_3	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338982	SP_HetCD_5	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338983	SP_HetCD_4	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338984	SP_HetCD_3	Serum	CHCHD10 S55L Het	Control Diet	250	F
SA338985	SL_HetHFD_2	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338986	SL_HetHFD_5	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338987	SL_HetHFD_6	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338988	SL_HetHFD_4	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338989	SL_HetHFD_3	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338990	SP_HetHFD_1	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338991	SL_HetHFD_1	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338992	SP_HetHFD_4	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338993	S_HetHFD_3	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338994	SP_HetHFD_2	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338995	S_HetHFD_4	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338996	S_HetHFD_5	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338997	S_HetHFD_2	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338998	S_HetHFD_1	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA338999	SP_HetHFD_3	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA339000	SP_HetHFD_5	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA339001	SP_HetHFD_6	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA339002	S_HetHFD_6	Serum	CHCHD10 S55L Het	High Fat Diet	250	F
SA339003	SP_WTCD_4	Serum	WT	Control Diet	250	F
SA339004	SP_WTCD_1	Serum	WT	Control Diet	250	F
SA339005	SP_WTCD_2	Serum	WT	Control Diet	250	F
SA339006	SP_WTCD_3	Serum	WT	Control Diet	250	F
SA339007	SP_WTCD_5	Serum	WT	Control Diet	250	F
SA339008	SP_WTCD_6	Serum	WT	Control Diet	250	F
SA339009	SL_WTCD_1	Serum	WT	Control Diet	250	F
SA339010	SL_WTCD_2	Serum	WT	Control Diet	250	F
SA339011	SL_WTCD_3	Serum	WT	Control Diet	250	F
SA339012	S_WTCD_2	Serum	WT	Control Diet	250	F
SA339013	S_WTCD_3	Serum	WT	Control Diet	250	F
SA339014	S_WTCD_5	Serum	WT	Control Diet	250	F
SA339015	S_WTCD_4	Serum	WT	Control Diet	250	F
SA339016	S_WTCD_6	Serum	WT	Control Diet	250	F
SA339017	SL_WTCD_4	Serum	WT	Control Diet	250	F
SA339018	SL_WTCD_5	Serum	WT	Control Diet	250	F
SA339019	S_WTCD_1	Serum	WT	Control Diet	250	F
SA339020	SL_WTCD_6	Serum	WT	Control Diet	250	F
SA339021	SP_WTHFD_6	Serum	WT	High Fat Diet	250	F
SA339022	SP_WTHFD_5	Serum	WT	High Fat Diet	250	F
SA339023	SP_WTHFD_1	Serum	WT	High Fat Diet	250	F
SA339024	SP_WTHFD_3	Serum	WT	High Fat Diet	250	F
SA339025	SP_WTHFD_2	Serum	WT	High Fat Diet	250	F
SA339026	SP_WTHFD_4	Serum	WT	High Fat Diet	250	F
SA339027	S_WTHFD_3	Serum	WT	High Fat Diet	250	F
SA339028	SL_WTHFD_2	Serum	WT	High Fat Diet	250	F
SA339029	SL_WTHFD_6	Serum	WT	High Fat Diet	250	F
SA339030	SL_WTHFD_5	Serum	WT	High Fat Diet	250	F
SA339031	SL_WTHFD_4	Serum	WT	High Fat Diet	250	F
SA339032	SL_WTHFD_1	Serum	WT	High Fat Diet	250	F
SA339033	S_WTHFD_6	Serum	WT	High Fat Diet	250	F
SA339034	S_WTHFD_2	Serum	WT	High Fat Diet	250	F
SA339035	SL_WTHFD_3	Serum	WT	High Fat Diet	250	F
SA339036	S_WTHFD_4	Serum	WT	High Fat Diet	250	F
SA339037	S_WTHFD_5	Serum	WT	High Fat Diet	250	F
SA339038	S_WTHFD_1	Serum	WT	High Fat Diet	250	F

Showing results 1 to 72 of 72

Showing results 1 to 72 of 72

Collection:

Collection ID:	CO003238
Collection Summary:	Blood was collected by cheek bleeds into serum separator tubes. Serum was separated after 30 minutes of clotting at room temperature and centrifugation at 2000xg for 15 min.
Sample Type:	Blood (serum)

Treatment:

Treatment ID:	TR003254
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).

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.

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

MS:

MS ID:	MS004864
Analysis ID:	AN005128
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).
Ion Mode:	UNSPECIFIED
Analysis Protocol File:	Serum_MS_and_Data_Analysis.pdf

MS ID:	MS004865
Analysis ID:	AN005129
Instrument Name:	Thermo Q Exactive Orbitrap
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Identification of free fatty acids was based on accurate masses within 5 ppm and standard retention times from compound standards. Relative quantitation was performed based on MS signal intensities.
Ion Mode:	NEGATIVE
Analysis Protocol File:	Serum_MS_and_Data_Analysis.pdf

MS ID:	MS004866
Analysis ID:	AN005130
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. 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:	Serum_MS_and_Data_Analysis.pdf