Summary of project PR001389
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
| 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 |
Summary of all studies in project PR001389
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002182 | Amelioration of developmental programming of NAFLD in weanling liver using PQQ | Mus musculus | University of Oklahoma Health Sciences Center | MS | 2023-04-20 | 1 | 9 | Not available |
| ST002191 | Amelioration of developmental programming of NAFLD in fetal liver using PQQ | Mus musculus | University of Oklahoma Health Sciences Center | MS | 2023-04-20 | 1 | 9 | Not available |
| ST002192 | Amelioration of developmental programming of NAFLD in adult liver using PQQ | Mus musculus | University of Oklahoma Health Sciences Center | MS* | 2023-04-20 | 1 | 84 | Uploaded data (970K) |
