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 |
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Collection:
| Collection ID: | CO002458 |
| Collection Summary: | Mice were deeply anesthetized and perfused intracardially with saline containing 1 mM MOPS (pH 7.4). Liver was rapidly removed, frozen on liquid nitrogen and stored at –80°C until further processing. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
