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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST002191 |
| Study Title | Amelioration of developmental programming of NAFLD in fetal liver using PQQ |
| Study Type | 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 |
| karen-jonscher@ouhsc.edu | |
| Phone | 3032294620 |
| Submit Date | 2022-04-20 |
| Num Groups | 3 |
| Total Subjects | 9 |
| Publications | Jonscher, et al FASEB J 2017; Friedman, et al Hepatol Commun 2018 |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-04-20 |
| Release Version | 1 |
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: | 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 |
|---|---|---|
| SA210172 | F1421 | CH |
| SA210173 | F1429 | CH |
| SA210174 | F1433 | CH |
| SA210175 | F1430 | HFD |
| SA210176 | F1423 | HFD |
| SA210177 | F1422 | HFD |
| SA210178 | F936 | HFDPQQ |
| SA210179 | F931 | HFDPQQ |
| SA210180 | F929 | HFDPQQ |
| 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 |
