Summary of project PR001529

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

Project ID: PR001529
Project DOI:doi: 10.21228/M8298N
Project Title:Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups
Project 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
Email:hirabayashi-tt@igakuken.or.jp
Phone:+81-3-5316-3100

Summary of all studies in project PR001529

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
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(* : Contains raw data)
ST002376 Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups(Pnpla8-knockout) Mus musculus Tokyo Metropolitan Institute of Medical Science MS 2022-12-15 1 12 Uploaded data (24.8K)
ST002377 Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups (Pnpla7-knockout) Mus musculus Tokyo Metropolitan Institute of Medical Science MS 2022-12-15 1 12 Uploaded data (24.8K)
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