Summary of Study ST002376
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 PR001529. The data can be accessed directly via it's Project DOI: 10.21228/M8298N 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.
| Study ID | ST002376 |
| Study Title | Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups(Pnpla8-knockout) |
| Study Summary | Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21, and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display a decreased hepatic triglyceride likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver. |
| Institute | Tokyo Metropolitan Institute of Medical Science |
| Last Name | Hirabayashi |
| First Name | Tetsuya |
| Address | 2-6-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan |
| hirabayashi-tt@igakuken.or.jp | |
| Phone | +81-3-5316-3100 |
| Submit Date | 2022-11-29 |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-12-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003871 | AN003872 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | CE | CE |
| Chromatography system | Agilent 7100 CE | Agilent 7100 CE |
| Column | Fused silica capillary i.d. 50 μm × 80 cm | Fused silica capillary i.d. 50 μm × 80 cm |
| MS Type | ESI | ESI |
| MS instrument type | Other | Other |
| MS instrument name | Agilent CE-TOFMS | Agilent CE-TOFMS |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
MS:
| MS ID: | MS003612 |
| Analysis ID: | AN003871 |
| Instrument Name: | Agilent CE-TOFMS |
| Instrument Type: | Other |
| MS Type: | ESI |
| MS Comments: | The spectrometer was scanned from m/z 50 to 1,000. Peaks were extracted using automatic integration software MasterHands (ver.2.16.0.15 Keio University). Signal peaks corresponding to isotopomers, adduct ions, and other product ions of known metabolites were excluded, and remaining peaks were annotated with putative metabolites from the HMT metabolite database based on their migration time and m/z values. Peak areas were normalized to internal standards and sample amounts. |
| Ion Mode: | POSITIVE |
| MS ID: | MS003613 |
| Analysis ID: | AN003872 |
| Instrument Name: | Agilent CE-TOFMS |
| Instrument Type: | Other |
| MS Type: | ESI |
| MS Comments: | The spectrometer was scanned from m/z 50 to 1,000. Peaks were extracted using automatic integration software MasterHands (ver.2.16.0.15 Keio University). Signal peaks corresponding to isotopomers, adduct ions, and other product ions of known metabolites were excluded, and remaining peaks were annotated with putative metabolites from the HMT metabolite database based on their migration time and m/z values. Peak areas were normalized to internal standards and sample amounts. |
| Ion Mode: | NEGATIVE |
