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 |
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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 |
