#METABOLOMICS WORKBENCH nsouthwell_20240306_164620 DATATRACK_ID:4691 STUDY_ID:ST003128 ANALYSIS_ID:AN005129 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 serum fatty acids, lipidome and metabolome in CHCHD10 ST:STUDY_TITLE 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 HetCD_1 S_HetCD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_1.raw SUBJECT_SAMPLE_FACTORS HetCD_2 S_HetCD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_2.raw SUBJECT_SAMPLE_FACTORS HetCD_3 S_HetCD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_3.raw SUBJECT_SAMPLE_FACTORS HetCD_4 S_HetCD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_4.raw SUBJECT_SAMPLE_FACTORS HetCD_5 S_HetCD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_5.raw SUBJECT_SAMPLE_FACTORS HetCD_6 S_HetCD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetCD_6.raw SUBJECT_SAMPLE_FACTORS HetCD_1 SL_HetCD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_1.raw SUBJECT_SAMPLE_FACTORS HetCD_2 SL_HetCD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_2.raw SUBJECT_SAMPLE_FACTORS HetCD_3 SL_HetCD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_3.raw SUBJECT_SAMPLE_FACTORS HetCD_4 SL_HetCD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_4.raw SUBJECT_SAMPLE_FACTORS HetCD_5 SL_HetCD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_5.raw SUBJECT_SAMPLE_FACTORS HetCD_6 SL_HetCD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetCD_6.raw SUBJECT_SAMPLE_FACTORS HetCD_1 SP_HetCD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_1.raw SUBJECT_SAMPLE_FACTORS HetCD_2 SP_HetCD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_2.raw SUBJECT_SAMPLE_FACTORS HetCD_3 SP_HetCD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_3.raw SUBJECT_SAMPLE_FACTORS HetCD_4 SP_HetCD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_4.raw SUBJECT_SAMPLE_FACTORS HetCD_5 SP_HetCD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_5.raw SUBJECT_SAMPLE_FACTORS HetCD_6 SP_HetCD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetCD_6.raw SUBJECT_SAMPLE_FACTORS HetHFD_1 S_HetHFD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_1.raw SUBJECT_SAMPLE_FACTORS HetHFD_2 S_HetHFD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_2.raw SUBJECT_SAMPLE_FACTORS HetHFD_3 S_HetHFD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_3.raw SUBJECT_SAMPLE_FACTORS HetHFD_4 S_HetHFD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_4.raw SUBJECT_SAMPLE_FACTORS HetHFD_5 S_HetHFD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_5.raw SUBJECT_SAMPLE_FACTORS HetHFD_6 S_HetHFD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_HetHFD_6.raw SUBJECT_SAMPLE_FACTORS HetHFD_1 SL_HetHFD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_1.raw SUBJECT_SAMPLE_FACTORS HetHFD_2 SL_HetHFD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_2.raw SUBJECT_SAMPLE_FACTORS HetHFD_3 SL_HetHFD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_3.raw SUBJECT_SAMPLE_FACTORS HetHFD_4 SL_HetHFD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_4.raw SUBJECT_SAMPLE_FACTORS HetHFD_5 SL_HetHFD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_5.raw SUBJECT_SAMPLE_FACTORS HetHFD_6 SL_HetHFD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_HetHFD_6.raw SUBJECT_SAMPLE_FACTORS HetHFD_1 SP_HetHFD_1 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_1.raw SUBJECT_SAMPLE_FACTORS HetHFD_2 SP_HetHFD_2 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_2.raw SUBJECT_SAMPLE_FACTORS HetHFD_3 SP_HetHFD_3 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_3.raw SUBJECT_SAMPLE_FACTORS HetHFD_4 SP_HetHFD_4 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_4.raw SUBJECT_SAMPLE_FACTORS HetHFD_5 SP_HetHFD_5 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_5.raw SUBJECT_SAMPLE_FACTORS HetHFD_6 SP_HetHFD_6 Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_HetHFD_6.raw SUBJECT_SAMPLE_FACTORS WTCD_1 SL_WTCD_1 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_1.raw SUBJECT_SAMPLE_FACTORS WTCD_2 SL_WTCD_2 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_2.raw SUBJECT_SAMPLE_FACTORS WTCD_3 SL_WTCD_3 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_3.raw SUBJECT_SAMPLE_FACTORS WTCD_4 SL_WTCD_4 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_4.raw SUBJECT_SAMPLE_FACTORS WTCD_5 SL_WTCD_5 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_5.raw SUBJECT_SAMPLE_FACTORS WTCD_6 SL_WTCD_6 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTCD_6.raw SUBJECT_SAMPLE_FACTORS WTCD_1 SP_WTCD_1 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_1.raw SUBJECT_SAMPLE_FACTORS WTCD_2 SP_WTCD_2 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_2.raw SUBJECT_SAMPLE_FACTORS WTCD_3 SP_WTCD_3 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_3.raw SUBJECT_SAMPLE_FACTORS WTCD_4 SP_WTCD_4 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_4.raw SUBJECT_SAMPLE_FACTORS WTCD_5 SP_WTCD_5 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_5.raw SUBJECT_SAMPLE_FACTORS WTCD_6 SP_WTCD_6 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTCD_6.raw SUBJECT_SAMPLE_FACTORS WTCD_1 S_WTCD_1 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_1.raw SUBJECT_SAMPLE_FACTORS WTCD_2 S_WTCD_2 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_2.raw SUBJECT_SAMPLE_FACTORS WTCD_3 S_WTCD_3 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_3.raw SUBJECT_SAMPLE_FACTORS WTCD_4 S_WTCD_4 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_4.raw SUBJECT_SAMPLE_FACTORS WTCD_5 S_WTCD_5 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_5.raw SUBJECT_SAMPLE_FACTORS WTCD_6 S_WTCD_6 Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTCD_6.raw SUBJECT_SAMPLE_FACTORS WTHFD_1 SL_WTHFD_1 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_1.raw SUBJECT_SAMPLE_FACTORS WTHFD_2 SL_WTHFD_2 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_2.raw SUBJECT_SAMPLE_FACTORS WTHFD_3 SL_WTHFD_3 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_3.raw SUBJECT_SAMPLE_FACTORS WTHFD_4 SL_WTHFD_4 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_4.raw SUBJECT_SAMPLE_FACTORS WTHFD_5 SL_WTHFD_5 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_5.raw SUBJECT_SAMPLE_FACTORS WTHFD_6 SL_WTHFD_6 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SL_WTHFD_6.raw SUBJECT_SAMPLE_FACTORS WTHFD_1 SP_WTHFD_1 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_1.raw SUBJECT_SAMPLE_FACTORS WTHFD_2 SP_WTHFD_2 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_2.raw SUBJECT_SAMPLE_FACTORS WTHFD_3 SP_WTHFD_3 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_3.raw SUBJECT_SAMPLE_FACTORS WTHFD_4 SP_WTHFD_4 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_4.raw SUBJECT_SAMPLE_FACTORS WTHFD_5 SP_WTHFD_5 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_5.raw SUBJECT_SAMPLE_FACTORS WTHFD_6 SP_WTHFD_6 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=SP_WTHFD_6.raw SUBJECT_SAMPLE_FACTORS WTHFD_1 S_WTHFD_1 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_1.raw SUBJECT_SAMPLE_FACTORS WTHFD_2 S_WTHFD_2 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_2.raw SUBJECT_SAMPLE_FACTORS WTHFD_3 S_WTHFD_3 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_3.raw SUBJECT_SAMPLE_FACTORS WTHFD_4 S_WTHFD_4 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_4.raw SUBJECT_SAMPLE_FACTORS WTHFD_5 S_WTHFD_5 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_5.raw SUBJECT_SAMPLE_FACTORS WTHFD_6 S_WTHFD_6 Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F RAW_FILE_NAME(Raw File Name)=S_WTHFD_6.raw #COLLECTION CO:COLLECTION_SUMMARY Blood was collected by cheek bleeds into serum separator tubes. Serum was CO:COLLECTION_SUMMARY separated after 30 minutes of clotting at room temperature and centrifugation at CO:COLLECTION_SUMMARY 2000xg for 15 min. CO:SAMPLE_TYPE Blood (serum) #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). #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Untargeted and targeted metabolomics: Serum metabolites were extracted with 80% SP:SAMPLEPREP_SUMMARY methanol. The extracts were clarified by centrifugation at 15,000 g for 10 min. SP:SAMPLEPREP_SUMMARY The supernatant was collected and dried down using a SpeedVac. For lipidomics SP:SAMPLEPREP_SUMMARY analyses: 180 µl of 90% isopropanol was added to 20 µl serum. Samples were SP:SAMPLEPREP_SUMMARY vortexed for 2 min, sonicated for 1 min using a probe sonicator and centrifuged SP:SAMPLEPREP_SUMMARY at 15,000 g for 10 min. The supernatant was collected and dried down using a SP:SAMPLEPREP_SUMMARY 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. Free Fatty Acids: Free fatty acids were extracted from serum using 90% SP:SAMPLEPREP_SUMMARY methanol (LC/MS grade, Thermo Scientific). The extracts were clarified by SP:SAMPLEPREP_SUMMARY centrifugation at 15,000 g for 10 min. The supernatant was collected and dried SP:SAMPLEPREP_SUMMARY down using a SpeedVac. The dried sample was reconstituted using 50% methanol SP:SAMPLEPREP_SUMMARY prior to LC-MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Serum free fatty acids CH:METHODS_FILENAME Serum_MS_and_Data_Analysis.pdf CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Imtakt Cadenza CD-C18 (150 x 2.1 mm, 3um) CH:COLUMN_TEMPERATURE 35 CH: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, CH:FLOW_GRADIENT followed by 5 min of re-equilibration CH:FLOW_RATE 150 µl/min CH:SOLVENT_A 100% water; 5 mM ammonium acetate CH:SOLVENT_B 85% isopropanol/10% acetonitrile/5% water; 5 mM ammonium acetate CH:CHROMATOGRAPHY_TYPE Reversed phase #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE Serum_MS_and_Data_Analysis.pdf #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:MS_COMMENTS Identification of free fatty acids was based on accurate masses within 5 ppm and MS:MS_COMMENTS standard retention times from compound standards. Relative quantitation was MS:MS_COMMENTS performed based on MS signal intensities. MS:ION_MODE NEGATIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak Intensity MS_METABOLITE_DATA_START Samples S_HetCD_1 S_HetCD_2 S_HetCD_3 S_HetCD_4 S_HetCD_5 S_HetCD_6 S_HetHFD_1 S_HetHFD_2 S_HetHFD_3 S_HetHFD_4 S_HetHFD_5 S_HetHFD_6 S_WTCD_1 S_WTCD_2 S_WTCD_3 S_WTCD_4 S_WTCD_5 S_WTCD_6 S_WTHFD_1 S_WTHFD_2 S_WTHFD_3 S_WTHFD_4 S_WTHFD_5 S_WTHFD_6 Factors Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:CHCHD10 S55L Het | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:Control Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F Sample source:Serum | Genotype:WT | Treatment:High Fat Diet | Age (d):250 | Sex:F C10:0 1615436.0000 1816009.0000 1404726.0000 1296044.0000 1353720.0000 1424486.0000 1039292.0000 1126998.0000 1316251.0000 1468373.0000 2567560.0000 1303946.0000 1351709.0000 1437451.0000 1864409.0000 1899434.0000 1097065.0000 1404920.0000 1354407.0000 2098626.0000 1328587.0000 1027701.0000 1335555.0000 1442718.0000 C12:0 9388222.0000 9318918.0000 6124065.0000 5447965.0000 6145193.0000 6366811.0000 3810643.0000 4293837.0000 4892644.0000 4605972.0000 8035300.0000 6296822.0000 5768855.0000 6369122.0000 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