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.

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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.

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Study IDST002376
Study TitleHepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups(Pnpla8-knockout)
Study SummaryCholine 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 NameHirabayashi
First NameTetsuya
Address2-6-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan
Emailhirabayashi-tt@igakuken.or.jp
Phone+81-3-5316-3100
Submit Date2022-11-29
Analysis Type DetailLC-MS
Release Date2022-12-15
Release Version1
Tetsuya Hirabayashi Tetsuya Hirabayashi
https://dx.doi.org/10.21228/M8298N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

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

Subject:

Subject ID:SU002465
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6N
Age Or Age Range:6-weeks old

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA237375KO3Pnpla8-knockout
SA237376KO4Pnpla8-knockout
SA237377KO6Pnpla8-knockout
SA237378KO2Pnpla8-knockout
SA237379KO5Pnpla8-knockout
SA237380KO1Pnpla8-knockout
SA237381WT3Wild-type
SA237382WT2Wild-type
SA237383WT4Wild-type
SA237384WT5Wild-type
SA237385WT6Wild-type
SA237386WT1Wild-type
Showing results 1 to 12 of 12

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℃

Treatment:

Treatment ID:TR002477
Treatment Summary:No treatment in this study.

Sample Preparation:

Sampleprep ID:SP002471
Sampleprep Summary:Tissues with internal standards were homogenized with ice-cold acetonitrile:water (50:50) and centrifuged at 2,300 × g for 5 min at 4 °C. The supernatant was filtered through a 5-kDa cut-off filter (Ultrafree-MC-PLHCC, Human Metabolome Technologies) at 9,100 × g for 2 h at 4 °C, dried in a centrifugal evaporator at 1,500 rpm at 1,000 Pa, and resuspended in 50 μl of ultrapure water before metabolome analysis.

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

Chromatography:

Chromatography ID:CH002869
Instrument Name:Agilent 7100 CE
Column Name:Fused silica capillary i.d. 50 μm × 80 cm
Chromatography Type:CE

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
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