{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002192","ANALYSIS_ID":"AN003588","VERSION":"1","CREATED_ON":"June 2, 2022, 7:25 am"}, "PROJECT":{"PROJECT_TITLE":"Protective effects of maternal PQQ on hepatic lipid metabolism throughout the lifespan: Adult Study","PROJECT_TYPE":"Diet study and fetal programming","PROJECT_SUMMARY":"Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric non-alcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism asso-ciated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH. Here, we used untargeted mass spectrometry-based lipidomics to delineate lipotoxic effects of WD on offspring liver and identify lipid targets of PQQ. PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero. Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring. PQQ exposure reduced the hepatic phosphatidylcho-line/phosphatidylethanolamine (PC/PE) ratio in WD-fed offspring and improved glucose toler-ance. Notably, levels of protective n − 3 polyunsaturated fatty acids (PUFAs) were elevated in offspring exposed to PQQ, beginning in utero, and the increase in n − 3 PUFAs persisted into adulthood. Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life.","INSTITUTE":"University of Oklahoma Health Sciences Center","DEPARTMENT":"Biochemistry and Molecular Biology, Harold Hamm Diabetes Center","LABORATORY":"Jonscher","LAST_NAME":"Jonscher","FIRST_NAME":"Karen","ADDRESS":"975 NE 10th Street BRC-N 362A, Oklahoma City, OK, 73104, USA","EMAIL":"karen-jonscher@ouhsc.edu","PHONE":"3032294620","FUNDING_SOURCE":"NIDDK"}, "STUDY":{"STUDY_TITLE":"Amelioration of developmental programming of NAFLD in adult liver using PQQ","STUDY_TYPE":"Pre-natal and Post-natal Diet and PQQ treatment","STUDY_SUMMARY":"Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric non-alcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism asso-ciated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH. Here, we used untargeted mass spectrometry-based lipidomics to delineate lipotoxic effects of WD on offspring liver and identify lipid targets of PQQ. PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero. Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring. PQQ exposure reduced the hepatic phosphatidylcho-line/phosphatidylethanolamine (PC/PE) ratio in WD-fed offspring and improved glucose toler-ance. Notably, levels of protective n − 3 polyunsaturated fatty acids (PUFAs) were elevated in offspring exposed to PQQ, beginning in utero, and the increase in n − 3 PUFAs persisted into adulthood. Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life.","INSTITUTE":"University of Oklahoma Health Sciences Center","DEPARTMENT":"Biochemistry and Molecular Biology, Harold Hamm Diabetes Center","LABORATORY":"Jonscher","LAST_NAME":"Jonscher","FIRST_NAME":"Karen","ADDRESS":"975 NE 10th Street BRC-N 362A, Oklahoma City, OK, 73104, USA","EMAIL":"karen-jonscher@ouhsc.edu","PHONE":"3032294620","NUM_GROUPS":"4","TOTAL_SUBJECTS":"24","NUM_MALES":"24","PUBLICATIONS":"Jonscher, et al FASEB J 2017; Friedman, et al Hepatol Commun 2018"}, "SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","AGE_OR_AGE_RANGE":"20-24 weeks","GENDER":"Male","ANIMAL_HOUSING":"Vivarium University of Colorado Anschutz Medical Campus","ANIMAL_LIGHT_CYCLE":"12/12","ANIMAL_FEED":"CH; 2019; Envigo, Indianapolis, IN or .D TD.88137; Envigo","ANIMAL_WATER":"Water or treated with 1.25 mg/L PQQ"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"-", "Sample ID":"1991A", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1991B", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1991C", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1996A", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1996B", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1996C", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1990A", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1990B", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"1990C", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"5329C", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"5329A", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"5329B", "Factors":{"Diet":"CTL"} }, { "Subject ID":"-", "Sample ID":"389A", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"389B", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"389C", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"330A", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"330B", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"330C", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"358A", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"358B", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"358C", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"333A", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"333B", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"333C", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"362A", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"362B", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"362C", "Factors":{"Diet":"CTL PQQ"} }, { "Subject ID":"-", "Sample ID":"754A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"754B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"754C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"1007A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"1007B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"1007C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"5328B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"5328C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"5328A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"372A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"372B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"372C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"386A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"386B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"386C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"361A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"361B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"361C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"989C", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"989A", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"989B", "Factors":{"Diet":"WD"} }, { "Subject ID":"-", "Sample ID":"773A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"773B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"773C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"768A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"768B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"768C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"901A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"901B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"901C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"767A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"767B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"767C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"703A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"703B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"703C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"756A", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"756B", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"756C", "Factors":{"Diet":"WD PQQ"} }, { "Subject ID":"-", "Sample ID":"179A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"179B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"179C", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"181A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"181B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"181C", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"743A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"743B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"743C", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"739A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"739B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"739C", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"727A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"727B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"727C", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"766A", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"766B", "Factors":{"Diet":"WD PQQ/WD"} }, { "Subject ID":"-", "Sample ID":"766C", "Factors":{"Diet":"WD PQQ/WD"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"Livers were excised and snap frozen then 10-15 mg aliquots sent to the West Coast Metabolomics Center for analysis following standard protocols.","SAMPLE_TYPE":"Liver","STORAGE_CONDITIONS":"-80℃","COLLECTION_VIALS":"Cryotubes","STORAGE_VIALS":"Cryotubes"}, "TREATMENT":{"TREATMENT_SUMMARY":"Dams and offspring were fed either chow (CH) or western-style diet (WD), with or without PQQ in drinking water. A subset of WD-exposed offspring were weaned onto WD without PQQ.","TREATMENT":"WD and PQQ","TREATMENT_COMPOUND":"BioPQQ","TREATMENT_ROUTE":"Drinking water, ad libitem","TREATMENT_DOSE":"1.25 mg/L","TREATMENT_DOSEDURATION":"17-21 weeks","TREATMENT_VEHICLE":"drinking water"}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Tissue was homogenized and lipids extracted following standard protocols at the WCMC. Samples were prepared in triplicate","SAMPLEPREP_PROTOCOL_FILENAME":"SP_Extraction_Protocol_for_liver_multi-omic.pdf"}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Agilent 1200","COLUMN_NAME":"Waters Acquity CSH C18 (100 x 2.1mm, 1.7um)","METHODS_FILENAME":"SOP_Lipidomic_Analysis_by_UPLC_QTOF.pdf"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS","ANALYSIS_PROTOCOL_FILE":"SOP_Lipidomic_Analysis_by_UPLC_QTOF.pdf"}, "MS":{"INSTRUMENT_NAME":"Agilent 6530 QTOF","INSTRUMENT_TYPE":"QTOF","MS_TYPE":"ESI","ION_MODE":"NEGATIVE","MS_COMMENTS":"See attached file","MS_RESULTS_FILE":"ST002192_AN003588_Results.txt UNITS:Peak area Has m/z:Yes Has RT:Yes RT units:Minutes"} }