Summary of Study ST002192

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 PR001389. The data can be accessed directly via it's Project DOI: 10.21228/M85T47 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.

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Study IDST002192
Study TitleAmelioration of developmental programming of NAFLD in adult liver using PQQ
Study TypePre-natal and Post-natal Diet and PQQ treatment
Study SummaryMaternal 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
DepartmentBiochemistry and Molecular Biology, Harold Hamm Diabetes Center
LaboratoryJonscher
Last NameJonscher
First NameKaren
Address975 NE 10th Street BRC-N 362A, Oklahoma City, OK, 73104, USA
Emailkaren-jonscher@ouhsc.edu
Phone3032294620
Submit Date2022-04-20
Num Groups4
Total Subjects24
Num Males24
PublicationsJonscher, et al FASEB J 2017; Friedman, et al Hepatol Commun 2018
Analysis Type DetailLC-MS
Release Date2023-04-20
Release Version1
Karen Jonscher Karen Jonscher
https://dx.doi.org/10.21228/M85T47
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001389
Project DOI:doi: 10.21228/M85T47
Project Title:Protective effects of maternal PQQ on hepatic lipid metabolism throughout the lifespan
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

Subject:

Subject ID:SU002278
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 WD; TD.88137; Envigo
Animal Water:Water or treated with 1.25 mg/L PQQ
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Diet
SA2101811990CCTL
SA2101825329ACTL
SA2101831991ACTL
SA2101841990BCTL
SA2101855329BCTL
SA2101865329CCTL
SA2101871991CCTL
SA2101881990ACTL
SA2101891996ACTL
SA2101901991BCTL
SA2101911996BCTL
SA2101921996CCTL
SA210193333ACTL PQQ
SA210194333BCTL PQQ
SA210195333CCTL PQQ
SA210196362BCTL PQQ
SA210197358CCTL PQQ
SA210198362CCTL PQQ
SA210199362ACTL PQQ
SA210200358ACTL PQQ
SA210201389BCTL PQQ
SA210202358BCTL PQQ
SA210203389ACTL PQQ
SA210204330ACTL PQQ
SA210205389CCTL PQQ
SA210206330BCTL PQQ
SA210207330CCTL PQQ
SA210208386AWD
SA210209386CWD
SA210210386BWD
SA210211361BWD
SA210212989BWD
SA210213372CWD
SA210214989AWD
SA210215989CWD
SA210216361CWD
SA210217361AWD
SA2102181007AWD
SA210219754CWD
SA210220754AWD
SA210221372BWD
SA2102221007BWD
SA210223754BWD
SA2102245328AWD
SA210225372AWD
SA2102265328CWD
SA2102271007CWD
SA2102285328BWD
SA210229703AWD PQQ
SA210230767BWD PQQ
SA210231767CWD PQQ
SA210232756BWD PQQ
SA210233767AWD PQQ
SA210234756CWD PQQ
SA210235756AWD PQQ
SA210236703CWD PQQ
SA210237703BWD PQQ
SA210238773CWD PQQ
SA210239773BWD PQQ
SA210240901CWD PQQ
SA210241768AWD PQQ
SA210242773AWD PQQ
SA210243901BWD PQQ
SA210244768BWD PQQ
SA210245901AWD PQQ
SA210246768CWD PQQ
SA210247727BWD PQQ/WD
SA210248739CWD PQQ/WD
SA210249727AWD PQQ/WD
SA210250766BWD PQQ/WD
SA210251739BWD PQQ/WD
SA210252766CWD PQQ/WD
SA210253766AWD PQQ/WD
SA210254727CWD PQQ/WD
SA210255181CWD PQQ/WD
SA210256179CWD PQQ/WD
SA210257179BWD PQQ/WD
SA210258179AWD PQQ/WD
SA210259181AWD PQQ/WD
SA210260181BWD PQQ/WD
SA210261743CWD PQQ/WD
SA210262743BWD PQQ/WD
SA210263743AWD PQQ/WD
SA210264739AWD PQQ/WD
Showing results 1 to 84 of 84

Collection:

Collection ID:CO002271
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 ID:TR002290
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

Sample Preparation:

Sampleprep ID:SP002284
Sampleprep Summary:Tissue was homogenized and lipids extracted following standard protocols at the WCMC. Samples were prepared in triplicate
Sampleprep Protocol Filename:OUHSC_SP_Extraction_Protocol_for_liver_multi-omic.pdf

Chromatography:

Chromatography ID:CH002651
Methods Filename:SOP_Lipidomic_Analysis_by_UPLC_QTOF.pdf
Instrument Name:Agilent 1200
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN003587
Analysis Type:MS
Analysis Protocol File:SOP_Lipidomic_Analysis_by_UPLC_QTOF.pdf
Chromatography ID:CH002651
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST002192_AN003587_Results.txt
Units:Peak area
  
Analysis ID:AN003588
Analysis Type:MS
Analysis Protocol File:SOP_Lipidomic_Analysis_by_UPLC_QTOF.pdf
Chromatography ID:CH002651
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST002192_AN003588_Results.txt
Units:Peak area
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