{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001092","ANALYSIS_ID":"AN001778","VERSION":"1","CREATED_ON":"November 6, 2018, 4:06 pm"}, "PROJECT":{"PROJECT_TITLE":"Metabolic approaches reveal the role of CAR in energy metabolism","PROJECT_TYPE":"Time Course","PROJECT_SUMMARY":"The constitutive androstane receptor (CAR; NR1I3) contributes important regulatory roles in biotransformation, xenobiotic transport function, energy metabolism and lipid homeostasis. In this investigation, global serum and liver tissue metabolomes were assessed analytically in wild type and CAR-null transgenic mice using NMR, GC/MS and UPLC/MS-MS-based metabolomics. Significantly, CAR activation increased serum levels of fatty acids, lactate, ketone bodies and tricarboxylic acid cycle products, whereas levels of phosphatidylcholine, sphingomyelin, amino acids and liver glucose were decreased following short-term activation of CAR. Mechanistically, quantitative mRNA analysis demonstrated significantly decreased expression of key gluconeogenic pathways, and increased expression of glucose utilization pathways, changes likely resulting from down-regulation of the hepatic glucose sensor and bi-directional transporter, Glut2. Short-term CAR activation also resulted in enhanced fatty acid synthesis and impaired β-oxidation. In summary, CAR contributes an expansive role regulating energy metabolism, significantly impacting glucose, and monocarboxylic acid, as well as fatty acid metabolism and lipid homeostasis, through receptor-mediated regulation of several genes in multiple associated pathways.","INSTITUTE":"Pennsylvania State University","LABORATORY":"Omiecinski Lab","LAST_NAME":"Omiecinski","FIRST_NAME":"Curt","ADDRESS":"101 Life Sciences Building","EMAIL":"cjo10@psu.edu, dmw178@psu.edu","PHONE":"8148651572"}, "STUDY":{"STUDY_TITLE":"Metabolic profiling by NMR analysis in liver aqueous extract samples","STUDY_TYPE":"Time Course","STUDY_SUMMARY":"Liver tissue were harvested from wild type and CAR knockout mice treated for 48 or 72h with or without TCPOBOP.","INSTITUTE":"Pennsylvania State University","LABORATORY":"Omiecinski Lab","LAST_NAME":"Omiecinski","FIRST_NAME":"Curt","ADDRESS":"101 Life Sciences Building","EMAIL":"cjo10@psu.edu, dmw178@psu.edu","PHONE":"8148651572","NUM_GROUPS":"8","TOTAL_SUBJECTS":"48","NUM_MALES":"48"}, "SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENOTYPE_STRAIN":"Wild Type C57BL/6 and CAR Knockout","AGE_OR_AGE_RANGE":"Approximately 8 weeks old","GENDER":"Male","ANIMAL_LIGHT_CYCLE":"12 h","ANIMAL_FEED":"ad libitum","ANIMAL_WATER":"ad libitum"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_101", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_102", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_103", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_104", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_105", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_48H_106", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_201", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_202", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_203", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_204", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_205", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_48H_206", "Factors":{"Genotype":"WT","Time Point (h)":"48","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_301", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_302", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_303", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_304", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_305", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_DMSO_72H_306", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"-"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_401", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_402", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_403", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_404", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_405", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} }, { "Subject ID":"-", "Sample ID":"WT_TCP_72H_406", "Factors":{"Genotype":"WT","Time Point (h)":"72","TCPOBOP (mg/kg)":"2"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"Liver tissue was snap-frozen in liquid nitrogen and stored at -80C.","SAMPLE_TYPE":"Liver","STORAGE_CONDITIONS":"-80℃"}, "TREATMENT":{"TREATMENT_SUMMARY":"Each mouse was treated with either a singel does of 2 mg/kg of Car agonist (TCPOBOP) or the vehicle control via intraperitoneal injection."}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Liver tissue was homogenized in a methanol-water mixture, dried and resuspended in phosphate buffer containing TSP-d4.","SAMPLEPREP_PROTOCOL_FILENAME":"NMR_metabolomics_protocol.pdf","PROCESSING_METHOD":"Homogenization","PROCESSING_STORAGE_CONDITIONS":"4℃","EXTRACTION_METHOD":"Methanol/Water","EXTRACT_STORAGE":"On ice","SAMPLE_RESUSPENSION":"D2O","SAMPLE_SPIKING":"TSP-d4"}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"-","INSTRUMENT_NAME":"-","COLUMN_NAME":"-"}, "ANALYSIS":{"ANALYSIS_TYPE":"NMR","LABORATORY_NAME":"Omiecinski Lab"}, "NM":{"INSTRUMENT_NAME":"Bruker Avance III","INSTRUMENT_TYPE":"FT-NMR","NMR_EXPERIMENT_TYPE":"Other","NMR_COMMENTS":"NOESYPR1D","SPECTROMETER_FREQUENCY":"600 MHz","NMR_SOLVENT":"D2O","NMR_RESULTS_FILE":"ST001092_AN001778_Results.txt UNITS:ppm"} }