Summary of Study ST002191

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.

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Study IDST002191
Study TitleAmelioration of developmental programming of NAFLD in fetal liver using PQQ
Study TypeDiet 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 Groups3
Total Subjects9
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

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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:SU002277
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Age Or Age Range:E18.5
Gender:Male and female
Animal Housing:Vivarium University of Colorado Anschutz Medical Campus
Animal Light Cycle:12/12
Animal Feed:CH; D12450B; Research Diets, New Brunswick, NJ, USA or HFD; D12451; Research Diets
Animal Water:Water or treated with 1.25 mg/L PQQ

Factors:

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

mb_sample_id local_sample_id Diet
SA210172F1421CH
SA210173F1429CH
SA210174F1433CH
SA210175F1430HFD
SA210176F1423HFD
SA210177F1422HFD
SA210178F936HFDPQQ
SA210179F931HFDPQQ
SA210180F929HFDPQQ
Showing results 1 to 9 of 9

Collection:

Collection ID:CO002270
Collection Summary:Livers were excised and snap frozen then sent to the Metabolomics Core at the University of Colorado Anschutz Medical Campus for analysis following standard protocols.
Sample Type:Liver
Storage Conditions:-80℃
Collection Vials:Cryotubes
Storage Vials:Cryotubes

Treatment:

Treatment ID:TR002289
Treatment Summary:Dams were fed either chow (CH) or high fat diet (HFD), with or without PQQ in drinking water.
Treatment:HFD and PQQ
Treatment Compound:BioPQQ
Treatment Route:Drinking water, ad libitem
Treatment Dose:1.25 mg/L
Treatment Doseduration:6 weeks
Treatment Vehicle:drinking water

Sample Preparation:

Sampleprep ID:SP002283
Sampleprep Summary:Tissue was homogenized and lipids extracted following standard protocols at the Metabolomics Core at the University of Colorado Anschutz Medical Campus.
Sampleprep Protocol Filename:Fetal_and_weanling_lipid_protocols.pdf

Combined analysis:

Analysis ID AN003586
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode UNSPECIFIED
Units Peak area

Chromatography:

Chromatography ID:CH002650
Chromatography Summary:The analytical platform employed a Vanquish UHPLC system (Thermo Fisher Scientific, San Jose, CA, USA) coupled online to a Q Exactive mass spectrometer (Thermo Fisher Scientific, San Jose, CA, USA). Lipidomics analyses were performed as described in previous method papers and application notes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640979/, https://www.haematologica.org/article/view/9990, https://pubmed.ncbi.nlm.nih.gov/31119660/
Methods Filename:Fetal_and_weanling_lipid_protocols.pdf
Instrument Name:Thermo Vanquish
Column Name:Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003341
Analysis ID:AN003586
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:See attached file
Ion Mode:UNSPECIFIED
Analysis Protocol File:Fetal_and_weanling_lipid_protocols.pdf
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