#METABOLOMICS WORKBENCH nsouthwell_20240306_145021 DATATRACK_ID:4690 STUDY_ID:ST003127 ANALYSIS_ID:AN005127
VERSION                          	1
CREATED_ON                       	03-22-2024
#PROJECT
PR:PROJECT_TITLE                 	High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice
PR:PROJECT_SUMMARY               	Mutations in CHCHD10, a mitochondrial protein with undefined functions, are
PR:PROJECT_SUMMARY               	associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice
PR:PROJECT_SUMMARY               	harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L)
PR:PROJECT_SUMMARY               	develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and
PR:PROJECT_SUMMARY               	proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts,
PR:PROJECT_SUMMARY               	mtISR is accompanied by a metabolic rewiring characterized by increased reliance
PR:PROJECT_SUMMARY               	on glycolysis rather than fatty acid oxidation. To counteract this metabolic
PR:PROJECT_SUMMARY               	rewiring, heterozygous S55L mice were subjected to chronic high fat diet (HFD)
PR:PROJECT_SUMMARY               	to decrease insulin sensitivity and glucose uptake and enhance fatty acid
PR:PROJECT_SUMMARY               	utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant
PR:PROJECT_SUMMARY               	hearts and significantly extended the survival of mutant female mice affected by
PR:PROJECT_SUMMARY               	severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that
PR:PROJECT_SUMMARY               	HFD increased fatty acid utilization and ameliorated cardiomyopathy markers.
PR:PROJECT_SUMMARY               	Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L
PR:PROJECT_SUMMARY               	heart, suggesting activation of quality control mechanisms. Overall, our
PR:PROJECT_SUMMARY               	findings indicate that metabolic therapy can be effective in mitochondrial
PR:PROJECT_SUMMARY               	cardiomyopathies associated with proteotoxic stress.
PR:INSTITUTE                     	Weill Cornell Medicine
PR:LAST_NAME                     	Southwell
PR:FIRST_NAME                    	Nneka
PR:ADDRESS                       	407 E 61st St
PR:EMAIL                         	nns4001@med.cornell.edu
PR:PHONE                         	646-962-8172
PR:DOI                           	http://dx.doi.org/10.21228/M8FD9G
#STUDY
ST:STUDY_TITLE                   	Effect of high fat diet on heart lipidome in CHCHD10 mutant mice
ST:STUDY_SUMMARY                 	Mutations in CHCHD10, a mitochondrial protein with undefined functions, are
ST:STUDY_SUMMARY                 	associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice
ST:STUDY_SUMMARY                 	harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L)
ST:STUDY_SUMMARY                 	develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and
ST:STUDY_SUMMARY                 	proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts,
ST:STUDY_SUMMARY                 	mtISR is accompanied by a metabolic rewiring characterized by increased reliance
ST:STUDY_SUMMARY                 	on glycolysis rather than fatty acid oxidation. To counteract this metabolic
ST:STUDY_SUMMARY                 	rewiring, heterozygous S55L mice were subjected to chronic high fat diet (HFD)
ST:STUDY_SUMMARY                 	to decrease insulin sensitivity and glucose uptake and enhance fatty acid
ST:STUDY_SUMMARY                 	utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant
ST:STUDY_SUMMARY                 	hearts and significantly extended the survival of mutant female mice affected by
ST:STUDY_SUMMARY                 	severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that
ST:STUDY_SUMMARY                 	HFD increased fatty acid utilization and ameliorated cardiomyopathy markers.
ST:STUDY_SUMMARY                 	Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L
ST:STUDY_SUMMARY                 	heart, suggesting activation of quality control mechanisms. Overall, our
ST:STUDY_SUMMARY                 	findings indicate that metabolic therapy can be effective in mitochondrial
ST:STUDY_SUMMARY                 	cardiomyopathies associated with proteotoxic stress.
ST:INSTITUTE                     	Weill Cornell Medicine
ST:LAST_NAME                     	Southwell
ST:FIRST_NAME                    	Nneka
ST:ADDRESS                       	407 E 61st St
ST:EMAIL                         	nns4001@med.cornell.edu
ST:PHONE                         	646-962-8172
ST:SUBMIT_DATE                   	2024-03-06
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_1	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_1.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_2	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_2.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_3	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_3.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_5	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_5.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_10	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_10.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_6	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_6.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_7	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_7.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetCD_8	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetCD_8.raw
SUBJECT_SAMPLE_FACTORS           	-	HetCD_mixneg	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HetCD_mixneg.raw
SUBJECT_SAMPLE_FACTORS           	-	HetCD_mixpos	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HetCD_mixpos.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_2	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_2.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_3	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_3.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_4	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_4.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_5	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_5.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_10	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_10.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_6	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_6.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_7	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_7.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_HetHFD_9	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_HetHFD_9.raw
SUBJECT_SAMPLE_FACTORS           	-	HetHFD_mixneg	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HetHFD_mixneg.raw
SUBJECT_SAMPLE_FACTORS           	-	HetHFD_mixpos	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HetHFD_mixpos.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_1	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_1.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_2	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_2.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_3	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_3.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_4	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_4.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_10	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_10.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_6	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_6.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_8	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_8.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTCD_9	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTCD_9.raw
SUBJECT_SAMPLE_FACTORS           	-	WTCD_mixneg	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=WTCD_mixneg.raw
SUBJECT_SAMPLE_FACTORS           	-	WTCD_mixpos	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=WTCD_mixpos.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_1	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_1.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_3	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_3.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_4	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_4.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_5	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_5.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_10	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_10.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_6	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_6.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_7	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_7.raw
SUBJECT_SAMPLE_FACTORS           	-	HL_WTHFD_8	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=HL_WTHFD_8.raw
SUBJECT_SAMPLE_FACTORS           	-	WTHFD_mixneg	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=WTHFD_mixneg.raw
SUBJECT_SAMPLE_FACTORS           	-	WTHFD_mixpos	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:N/A | Age:75	RAW_FILE_NAME(Named Raw File_Heart Lipidomics)=WTHFD_mixpos.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Murine heart tissue was excised and snap frozen in liquid N2.
CO:SAMPLE_TYPE                   	Heart
#TREATMENT
TR:TREATMENT_SUMMARY             	CHCHD10 WT and CHCHD10 S55L heterozygous mice were treated with either a control
TR:TREATMENT_SUMMARY             	diet (70% Carbohydrate, 20% Protein, 10% Fat) or High Fat Diet (60% Fat, 20%
TR:TREATMENT_SUMMARY             	Protein, 20% Carbohydrate) in utero until 75 days of age.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	In brief, 1 ml of 90% isopropanol was added to 15 mg of homogenized heart
SP:SAMPLEPREP_SUMMARY            	tissue. Samples were vortexed for 2 min, sonicated for 1 min using a probe
SP:SAMPLEPREP_SUMMARY            	sonicator and centrifuged at 15,000 g for 10 min. The supernatant was collected
SP:SAMPLEPREP_SUMMARY            	and dried down using a SpeedVac. The dried samples were reconstituted using
SP:SAMPLEPREP_SUMMARY            	acetonitrile/isopropanol/water 65:30:5 containing stable isotope labeled
SP:SAMPLEPREP_SUMMARY            	internal lipid standards (Splash Lipidomix, Avanti Polar Lipids) prior to LC-MS
SP:SAMPLEPREP_SUMMARY            	analysis.
#CHROMATOGRAPHY
CH:METHODS_FILENAME              	Method_Lipidomics.pdf
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Imtakt Cadenza CD-C18 (150 x 2.1mm, 3um)
CH:COLUMN_TEMPERATURE            	35
CH: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;
CH:FLOW_GRADIENT                 	8-11 min, 58-66% B; 11-14 min, 66-70% B; 14-18 min, 70-75% B; 21-25 min,
CH:FLOW_GRADIENT                 	isocratic 97% B, 25-25.1 min 97-32% B
CH:FLOW_RATE                     	200 µl/min
CH:SOLVENT_A                     	60% acetonitrile/40% water; 10 mM ammonium formate; 0.1% formic acid
CH:SOLVENT_B                     	90% isopropanol/10% acetonitrile; 10 mM ammonium formate; 0.1% formic acid
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
AN:ANALYSIS_PROTOCOL_FILE        	Method_Lipidomics.pdf
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:MS_COMMENTS                   	A data-dependent mass spectrometric acquisition method was used for lipid
MS:MS_COMMENTS                   	identification. In this method, each MS survey scan was followed by up to 10
MS:MS_COMMENTS                   	MS/MS scans performed on the most abundant ions. Data was acquired in positive
MS:MS_COMMENTS                   	and negative mode in separate runs. The following electrospray parameters were
MS:MS_COMMENTS                   	used: spray voltage 3.0 kV, heated capillary temperature 350 °C, HESI probe
MS:MS_COMMENTS                   	temperature 350 °C, sheath gas, 35 units; auxiliary gas 10 units. For MS
MS:MS_COMMENTS                   	scans: resolution, 70,000 (at m/z 200); automatic gain control target, 3e6;
MS:MS_COMMENTS                   	maximum injection time, 200 ms; scan range, 250-1800 m/z. For MS/MS scans:
MS:MS_COMMENTS                   	resolution, 17,500 (at 200 m/z); automatic gain control target, 1e5 ions;
MS:MS_COMMENTS                   	maximum injection time, 75 ms; isolation window, 1 m/z; NCE, stepped 20,30 and
MS:MS_COMMENTS                   	40. The LC-MS results were processed using MS-DIAL software (version 4.9) for
MS:MS_COMMENTS                   	lipid identification and relative quantitation.
MS:ION_MODE                      	NEGATIVE
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS         	Peak Intensity
MS_METABOLITE_DATA_START
Samples	HL_HetCD_1	HL_HetCD_2	HL_HetCD_3	HL_HetCD_5	HL_HetCD_10	HL_HetCD_6	HL_HetCD_7	HL_HetCD_8	HL_HetHFD_2	HL_HetHFD_3	HL_HetHFD_4	HL_HetHFD_5	HL_HetHFD_10	HL_HetHFD_6	HL_HetHFD_7	HL_HetHFD_9	HL_WTCD_1	HL_WTCD_2	HL_WTCD_3	HL_WTCD_4	HL_WTCD_10	HL_WTCD_6	HL_WTCD_8	HL_WTCD_9	HL_WTHFD_1	HL_WTHFD_3	HL_WTHFD_4	HL_WTHFD_5	HL_WTHFD_10	HL_WTHFD_6	HL_WTHFD_7	HL_WTHFD_8
Factors	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:Control Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:F | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	Sample source:Heart | Genotype:WT | Treatment:High Fat Diet | Sex:M | Age:75	
CL 71:4	249820.0000	229648.9000	203268.5000	199999.4000	207130.0000	284321.2000	199918.2000	179238.3000	120774.5000	163383.0000	165138.0000	210518.3000	161388.9000	218277.3000	189829.4000	172392.6000	176349.5000	100835.7000	228270.2000	117705.5000	123938.6000	85445.8200	111329.0000	100760.2000	213472.7000	99127.3400	166941.7000	194239.8000	137698.1000	171400.6000	162149.9000	132275.4000
CL 72:5	20448060.0000	17578310.0000	22884280.0000	17601180.0000	16699030.0000	19708870.0000	23287500.0000	16832500.0000	11741630.0000	15532100.0000	12219370.0000	15416590.0000	13724950.0000	13050730.0000	13321830.0000	11182710.0000	16075250.0000	12675350.0000	19109450.0000	16532860.0000	12325820.0000	12045130.0000	14539330.0000	12557260.0000	18498370.0000	10769700.0000	13761630.0000	13636890.0000	11437140.0000	13801110.0000	12873220.0000	11745060.0000
CL 72:6	51616850.0000	44460520.0000	59029200.0000	45256760.0000	45835690.0000	49090140.0000	61987390.0000	42463980.0000	32722100.0000	41217940.0000	33250970.0000	42999840.0000	37305870.0000	37356250.0000	34988320.0000	29803120.0000	44393880.0000	33154680.0000	46860930.0000	43988040.0000	34046080.0000	33727500.0000	41343590.0000	33007830.0000	47710390.0000	30965490.0000	37910600.0000	34707500.0000	30661870.0000	39069980.0000	36385040.0000	34167440.0000
CL 72:7	109416800.0000	88358060.0000	104645400.0000	89504320.0000	91756380.0000	97494720.0000	98320020.0000	83192710.0000	60481530.0000	119587300.0000	79080810.0000	96833060.0000	105539800.0000	113851800.0000	84355410.0000	83162470.0000	108327500.0000	90244430.0000	93397030.0000	109151700.0000	121468200.0000	97155290.0000	113479700.0000	75461500.0000	102887200.0000	92646500.0000	116089100.0000	71005060.0000	111678000.0000	112124900.0000	115066000.0000	110709600.0000
CL 72:8	148014300.0000	119941300.0000	180696700.0000	130995400.0000	170642300.0000	146136300.0000	197348100.0000	117004500.0000	123638000.0000	233013900.0000	194323800.0000	214570200.0000	233011200.0000	257789600.0000	224114700.0000	169911100.0000	203813000.0000	146157400.0000	111457900.0000	176832400.0000	225011100.0000	250215500.0000	300686900.0000	173869100.0000	259904700.0000	256984300.0000	242654500.0000	88008780.0000	323904400.0000	270027800.0000	238282600.0000	249365600.0000
CL 72:9	5890368.0000	4380067.0000	7261860.0000	5378734.0000	7859353.0000	6598633.0000	7371385.0000	4811616.0000	2620477.0000	5372885.0000	3796932.0000	6477955.0000	4749925.0000	5948133.0000	4442545.0000	3522406.0000	8483990.0000	6335526.0000	4628775.0000	5762383.0000	9329296.0000	9764944.0000	12372960.0000	5494616.0000	5163675.0000	5438603.0000	6391103.0000	2240792.0000	5663330.0000	5726653.0000	5703782.0000	5561242.0000
CL 73:8	279382.4000	233936.8000	341350.0000	248572.8000	248774.6000	257183.5000	298724.2000	163769.6000	202650.7000	252993.7000	249823.3000	284762.4000	265587.8000	278579.3000	219173.5000	195199.0000	361208.2000	270321.9000	281401.6000	316115.0000	357578.2000	388102.2000	472459.7000	280926.8000	267085.9000	346440.7000	440317.0000	226808.6000	341227.0000	379064.3000	384317.1000	323776.6000
CL 74:10	8676736.0000	6378336.0000	11483040.0000	7629787.0000	8222089.0000	6946429.0000	8761914.0000	5247686.0000	7444377.0000	12587330.0000	9410452.0000	10622740.0000	11961470.0000	9698686.0000	8985995.0000	8104546.0000	13809160.0000	9872661.0000	10403240.0000	10445640.0000	10417070.0000	12111750.0000	17440930.0000	9422907.0000	10874320.0000	12602840.0000	14205790.0000	7766667.0000	11438570.0000	12568870.0000	13336910.0000	11881520.0000
CL 74:11	1994553.0000	2043849.0000	2500092.0000	1938135.0000	2243356.0000	2052039.0000	2200379.0000	2085036.0000	2097412.0000	2136754.0000	2029169.0000	2101411.0000	2167047.0000	1886877.0000	2146165.0000	2050652.0000	6296110.0000	3775117.0000	4066451.0000	4539893.0000	3656342.0000	3140032.0000	4438327.0000	2701849.0000	2255292.0000	2388897.0000	1878020.0000	1769962.0000	2084236.0000	1861955.0000	2039596.0000	2228711.0000
CL 74:6	3449269.0000	3472469.0000	3446969.0000	3517155.0000	3318658.0000	3625552.0000	3308110.0000	2947809.0000	4716936.0000	6612603.0000	5696448.0000	7109180.0000	5430174.0000	5600147.0000	6079920.0000	5231728.0000	4417277.0000	3958760.0000	4940586.0000	3969491.0000	3920215.0000	4729897.0000	5599738.0000	3926982.0000	8099174.0000	6424127.0000	9627986.0000	7616415.0000	7653853.0000	9253276.0000	7574450.0000	7507211.0000
CL 74:7	8839451.0000	8833805.0000	9858239.0000	8413030.0000	8542794.0000	9490805.0000	8650844.0000	7565099.0000	11962490.0000	16844230.0000	14192450.0000	17460600.0000	13903100.0000	14388230.0000	15351290.0000	12814880.0000	11436250.0000	9969196.0000	12330690.0000	10361760.0000	10466880.0000	11608600.0000	14728610.0000	9959292.0000	20066120.0000	16905220.0000	23858270.0000	18880650.0000	18981310.0000	23222110.0000	19409360.0000	18583720.0000
CL 74:8	16975360.0000	16844640.0000	20790270.0000	18130600.0000	17563670.0000	18183860.0000	22870920.0000	11047100.0000	22540170.0000	28281060.0000	26251720.0000	36540140.0000	28484600.0000	32117150.0000	29453190.0000	24821650.0000	24133120.0000	20197950.0000	19698040.0000	22030510.0000	21382290.0000	23062250.0000	29271550.0000	18597110.0000	33880550.0000	39350980.0000	52017540.0000	24678450.0000	50557890.0000	56509290.0000	43410240.0000	46127620.0000
CL 74:9	25859930.0000	22097740.0000	39779710.0000	26496820.0000	31799460.0000	26637820.0000	37621720.0000	17223330.0000	17509270.0000	29272520.0000	25698360.0000	23346080.0000	28995900.0000	26833740.0000	21375230.0000	18722890.0000	38139120.0000	25939680.0000	22590160.0000	29205500.0000	42450400.0000	46101060.0000	57388550.0000	28354720.0000	26229430.0000	25706130.0000	29221240.0000	20536060.0000	30689070.0000	30591020.0000	37846340.0000	35094330.0000
CL 76:10	6293482.0000	5363196.0000	8550371.0000	6596917.0000	5705250.0000	4789726.0000	6303783.0000	2695686.0000	4354496.0000	5074190.0000	4870677.0000	4191415.0000	6751966.0000	4245954.0000	3373369.0000	4293005.0000	14585960.0000	10061810.0000	16986640.0000	13736870.0000	10035840.0000	8033504.0000	13219740.0000	8782501.0000	6451864.0000	6156251.0000	8964333.0000	10636600.0000	5762375.0000	5991380.0000	8737127.0000	8844654.0000
CL 76:11	8954858.0000	7561479.0000	15993590.0000	8252519.0000	5997606.0000	5056546.0000	8918012.0000	3386544.0000	7757980.0000	11138450.0000	10284400.0000	7224010.0000	12008670.0000	7721615.0000	6510208.0000	6894630.0000	29840400.0000	20692970.0000	34995680.0000	27244630.0000	21482110.0000	17608960.0000	20508440.0000	13186070.0000	11741790.0000	13780860.0000	17352070.0000	22909480.0000	12610670.0000	15526820.0000	19317420.0000	16519200.0000
CL 76:12	19086190.0000	14592120.0000	28606050.0000	17180210.0000	13863270.0000	10538230.0000	19260610.0000	5164437.0000	14935170.0000	22572870.0000	21765080.0000	16789680.0000	25550630.0000	15245010.0000	13898590.0000	14404110.0000	68335940.0000	46322050.0000	54399130.0000	58019370.0000	50070420.0000	40121200.0000	57421720.0000	34866920.0000	24262460.0000	33165670.0000	45205930.0000	29043160.0000	31858500.0000	32641370.0000	49620980.0000	39944830.0000
CL 78:13	2546234.0000	2447926.0000	4502755.0000	2705375.0000	2036964.0000	1406288.0000	2504406.0000	633611.6000	1799727.0000	2037355.0000	1932517.0000	1061548.0000	3390908.0000	972859.1000	1064595.0000	1062557.0000	8241298.0000	5587208.0000	7590325.0000	6753710.0000	6535251.0000	4952406.0000	6092288.0000	5153679.0000	2758807.0000	2336509.0000	3199038.0000	4406047.0000	1965676.0000	1912222.0000	4282382.0000	4108983.0000
PA 34:3	109522.4000		617630.1000		73448.2900	15977.5100	35115.9300	12413.0100	49466.3600	19344.4800		92616.5300	131273.3000	17871.8600	12065.9400	12714.2000			48017.7300		18901.2700	43757.7400	90453.6200		81091.1200	696917.9000	27284.1400			16914.4600	23374.6000	436175.5000
PG 33:1	178222.0000	166549.5000	189852.8000	191052.8000	153049.7000	208141.2000	297715.3000	135254.0000	151322.6000	105606.7000	99622.9100	112032.6000	100475.7000	150964.2000	144033.6000	99131.3800	294000.4000	140688.1000	164277.0000	219350.4000	211545.8000	276723.4000	214622.8000	106776.0000	200000.2000	49764.5100	195946.9000	89980.3900	126348.8000	115446.0000	75094.5700	90511.9500
PG 34:0	19408000.0000	18582850.0000	19119380.0000	22457590.0000	25651840.0000	29014820.0000	29117650.0000	23702140.0000	20352430.0000	29332270.0000	26695220.0000	33260000.0000	28235340.0000	39904060.0000	28315000.0000	27978520.0000	18832820.0000	16339190.0000	17372870.0000	18265440.0000	25087590.0000	31074590.0000	26307860.0000	22288100.0000	27268870.0000	30301390.0000	41605900.0000	15289700.0000	39985510.0000	33144310.0000	36976800.0000	42887010.0000
PG 34:1	75133830.0000	63157300.0000	87747800.0000	74837560.0000	62938800.0000	77560920.0000	73758190.0000	49179570.0000	52834220.0000	77643650.0000	68781970.0000	74930020.0000	65939700.0000	87320270.0000	66689440.0000	58859670.0000	120290100.0000	81093210.0000	101608200.0000	92705140.0000	87457820.0000	102727200.0000	108480600.0000	78345660.0000	76513160.0000	63790580.0000	100349900.0000	68979660.0000	89611510.0000	93557510.0000	84722640.0000	77820660.0000
PG 34:2	11568390.0000	7569078.0000	13437420.0000	9579489.0000	14241250.0000	13080320.0000	13940460.0000	8798751.0000	8731249.0000	15858530.0000	14616890.0000	16560400.0000	16905750.0000	19458180.0000	14043260.0000	9904326.0000	20170850.0000	13223570.0000	12680990.0000	20131150.0000	24408480.0000	34437820.0000	38075510.0000	16720890.0000	15991510.0000	18504070.0000	27576910.0000	8907707.0000	30331980.0000	32851330.0000	22309270.0000	24665810.0000
PG 34:3	567647.3000	311690.9000	322414.1000	273784.6000	425465.7000	520981.5000	512392.7000	647840.9000	49667.9900	98659.5300	56979.0300	135335.5000	73775.3000	148210.2000	102240.6000	72955.7300	45644.0400	20545.6900	32805.8300	56856.6400	35432.0700	76353.9700	77350.9600	73569.7200	76007.3900	26887.2600	37634.1300	19010.4700	32991.5800	31235.0300	33822.3900	26182.6700
PG 36:1	34224220.0000	31626340.0000	44870770.0000	21276180.0000	15868900.0000	34363040.0000	34473540.0000	18810900.0000	44991140.0000	52025120.0000	55320490.0000	59561340.0000	58789570.0000	29695000.0000	42505000.0000	30339350.0000	116041700.0000	80128870.0000	99017180.0000	89891390.0000	86170340.0000	75875300.0000	107108900.0000	56286300.0000	73096500.0000	78143710.0000	60958900.0000	113205200.0000	107998800.0000	94710620.0000	92377040.0000	63460670.0000
PG 36:2	25154290.0000	12872260.0000	10519170.0000	8300091.0000	11794300.0000	15097550.0000	12582060.0000	15045000.0000	2715659.0000	8008867.0000	4640645.0000	7986600.0000	4341640.0000	10505390.0000	7890587.0000	6277726.0000	2084169.0000	1026431.0000	1943743.0000	2428520.0000	1316136.0000	2060820.0000	1932164.0000	1856180.0000	6147342.0000	1875091.0000	2875378.0000	1191533.0000	2357966.0000	2903475.0000	2511856.0000	2047320.0000
PG 36:3	13930660.0000	8368834.0000	7594743.0000	5994046.0000	10068170.0000	10311990.0000	9934257.0000	14341700.0000	2722062.0000	7596366.0000	4728182.0000	8826290.0000	4258338.0000	9557005.0000	8267194.0000	5481727.0000	1378008.0000	639947.4000	869510.7000	1413083.0000	922558.9000	1256338.0000	1395133.0000	1225288.0000	5336471.0000	1570755.0000	1972145.0000	965759.1000	1987841.0000	2399254.0000	1842566.0000	1507831.0000
PG 36:4	574099.4000	1028126.0000	406805.0000	1831311.0000	666382.1000	1726166.0000	879113.8000	1448193.0000	251292.0000	1345530.0000	1828028.0000	489228.6000	455311.8000	1473843.0000	1232651.0000	948559.1000	2231270.0000	1333400.0000	315975.7000	1306059.0000	795642.9000	749546.6000	739005.4000	862021.6000	823504.9000	279327.3000	1267775.0000	844845.2000	2012186.0000	1428628.0000	798617.4000	453823.3000
PG 36:5	221428.7000	166247.6000	152631.0000	149484.1000	361081.4000	297912.0000	245882.8000	436566.3000	65683.3100	215627.2000	146224.9000	290837.6000	100457.0000	281684.0000	213467.5000	146670.0000	25235.8500	9861.2790	18136.5600	24207.2100	25966.1400	27923.6100	32707.5600	24110.7800	148103.9000	41874.4200	61033.7300	19864.3100	57661.0300	67877.2800	43745.1300	35646.5000
PG 38:2	675936.9000	383831.8000	341291.0000	356212.3000	558971.2000	777088.4000	995422.4000	541344.5000	139561.4000	363376.6000	305656.8000	368299.1000	283892.6000	475510.0000	358407.9000	321482.2000	109053.7000		112077.5000	118918.0000	122849.3000	203943.6000	199107.3000	150600.2000	295426.6000	144718.8000	138815.7000	84870.1600	156572.1000	135369.8000	175479.2000	140767.0000
PG 38:5	805521.3000	478627.2000	622951.3000	519076.9000	568322.7000	464278.2000	484276.1000	475573.2000	263340.3000	489514.7000	509080.4000	811465.0000	579262.6000	458623.6000	435747.2000	332015.7000	478863.9000	327623.1000	344070.9000	357217.6000	283315.2000	292344.7000	387295.9000	232249.7000	530593.4000	443098.7000	707761.6000	231718.0000	416781.4000	373819.7000	339021.4000	273462.8000
PG 40:6	1208964.0000	914124.7000	807494.9000	761635.1000	903633.4000	1035466.0000	1130811.0000	847264.8000	164362.8000	469706.1000	384199.4000	847992.5000	434077.5000	512013.7000	631235.2000	557243.9000	621551.9000	362203.2000	703642.9000	464016.8000	609439.5000	502155.1000	741566.5000	367920.6000	428089.4000	286466.6000	352805.2000	136992.8000	288552.0000	292898.4000	270765.8000	184350.0000
PG 40:7	1643436.0000	1028528.0000	859760.8000	841713.5000	568130.3000	686392.3000	902528.9000	659807.7000	428127.0000	618288.8000	645060.1000	865654.8000	757720.1000	677428.4000	473738.3000	380646.3000	1027479.0000	644728.4000	911919.9000	555190.2000	435110.6000	405688.4000	627643.3000	348696.0000	750239.5000	261061.3000	507764.5000	415933.1000	340890.4000	249639.7000	335026.2000	285527.4000
PG 40:8	826217.4000	652483.3000	561671.3000	650433.6000	518896.6000	513702.8000	633260.3000	582534.2000	417188.6000	635584.9000	635944.7000	834876.4000	675490.0000	732648.2000	332847.6000	236476.0000	642852.4000	402949.3000	530425.7000	294868.3000	354212.7000	280700.7000	427736.5000	244246.7000	688962.4000	223274.0000	456480.3000	402988.9000	360077.8000	244709.7000	325116.3000	219231.2000
PG 42:10	363179.0000	218392.5000	278778.6000	224549.5000	200462.1000	171920.4000	189369.7000	188588.1000	146659.8000	218986.4000	180528.7000	285011.7000	289892.6000	213555.5000	147403.1000	135329.0000	306687.7000	234769.9000	324556.0000	124242.0000	151444.3000	91703.5100	163403.5000	90380.9900	224465.5000	98736.9400	211537.3000	223612.0000	115162.4000	80769.7400	91947.2900	91545.6100
PG 42:9	184668.4000	136375.3000	221921.2000	146571.8000	247154.0000	188738.8000	194239.7000	191661.3000	49453.9400	103092.1000	86951.1400	268416.8000	139380.5000	108723.4000	163110.1000	179463.4000	111999.8000	75180.7700	158135.9000	67706.7400	129734.8000	79932.2000	128980.0000	63015.3400	111218.5000	101281.1000	100893.1000	53305.5000	71900.1100	69437.5400	45966.4000	47093.8800
PG 44:11	282704.8000	269454.6000	253245.2000	200726.6000	181857.2000	232063.6000	245796.0000	181284.9000	110647.5000	139172.4000	112351.1000	255282.7000	193144.9000	150420.6000	145516.3000	163406.2000	337912.9000	217671.3000	717477.1000	128548.4000	228021.4000	161062.8000	260739.0000	136027.1000	145259.8000	81210.5800	129149.8000	184135.4000	112473.5000	89406.9600	90036.1300	73989.8000
PG 44:12	400931.3000	263523.6000	228895.0000	186126.2000	109137.1000	126005.9000	132081.7000	109828.0000	213977.7000	171344.0000	158862.6000	191726.3000	292650.8000	145679.2000	81130.4900	86423.6800	543640.6000	369278.3000	1172088.0000	190000.5000	181479.4000	120174.6000	215900.3000	145641.4000	209248.6000	65399.9000	171387.3000	729690.6000	138064.0000	79793.5000	107785.0000	112165.2000
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	pubchem_id	inchi_key	kegg_id	other_id	other_id_type	ri	ri_type	moverz_quant	
CL 71:4									
CL 72:5									
CL 72:6									
CL 72:7									
CL 72:8									
CL 72:9									
CL 73:8									
CL 74:10									
CL 74:11									
CL 74:6									
CL 74:7									
CL 74:8									
CL 74:9									
CL 76:10									
CL 76:11									
CL 76:12									
CL 78:13									
PA 34:3									
PG 33:1									
PG 34:0									
PG 34:1									
PG 34:2									
PG 34:3									
PG 36:1									
PG 36:2									
PG 36:3									
PG 36:4									
PG 36:5									
PG 38:2									
PG 38:5									
PG 40:6									
PG 40:7									
PG 40:8									
PG 42:10									
PG 42:9									
PG 44:11									
PG 44:12									
METABOLITES_END
#END