Summary of Study ST002303

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 PR001476. The data can be accessed directly via it's Project DOI: 10.21228/M8XT5F 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 IDST002303
Study TitleFitm2 is required for ER homeostasis and normal function of murine liver
Study SummaryThe ER-resident protein fat-inducing transcript 2 (FIT2) catalyzes acyl-CoA cleavage in vitro and is required for endoplasmic reticulum (ER) homeostasis and normal lipid storage in cells. The gene encoding FIT2 is essential for the viability of mice and worms. Whether FIT2 acts as an acyl-CoA diphosphatase in vivo and how this activity affects liver, where the protein was discovered, are unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice fed a chow diet exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. These mice also had more triglycerides in their livers than control littermates due, in part, to impaired secretion of triglyceride-rich lipoproteins and reduced capacity for fatty acid oxidation. Challenging FIT2-LKO mice with a high-fat diet worsened hepatic ER stress and liver injury, but unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings support the model that FIT2 acts as an acyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in murine liver.
Institute
Harvard School of Public Health
Last NameBond
First NameLaura
Address665 Huntington Ave., Building 2, 3rd Floor, Room 311 | Boston, MA 02115
Emaillaurabond44@gmail.com
Phone8573087183
Submit Date2022-09-17
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2022-10-26
Release Version1
Laura Bond Laura Bond
https://dx.doi.org/10.21228/M8XT5F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001476
Project DOI:doi: 10.21228/M8XT5F
Project Title:Fitm2 is required for ER homeostasis and normal function of murine liver
Project Summary:The ER-resident protein fat-inducing transcript 2 (FIT2) catalyzes acyl-CoA cleavage in vitro and is required for endoplasmic reticulum (ER) homeostasis and normal lipid storage in cells. The gene encoding FIT2 is essential for the viability of mice and worms. Whether FIT2 acts as an acyl-CoA diphosphatase in vivo and how this activity affects liver, where the protein was discovered, are unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice fed a chow diet exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. These mice also had more triglycerides in their livers than control littermates due, in part, to impaired secretion of triglyceride-rich lipoproteins and reduced capacity for fatty acid oxidation. Challenging FIT2-LKO mice with a high-fat diet worsened hepatic ER stress and liver injury, but unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings support the model that FIT2 acts as an acyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in murine liver.
Institute:Harvard University
Department:Molecular Metabolism
Laboratory:FareseWalther's lab
Last Name:Bond
First Name:Laura
Address:655 Huntington Avenue, Building 1, Room 203, Boston, MA, 02115, USA
Email:laurabond44@gmail.com
Phone:+18573087183

Subject:

Subject ID:SU002389
Subject Type:Mammal
Subject Species:Mus musculus

Factors:

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

mb_sample_id local_sample_id Genotype
SA226657BlankBlank
SA226664FIT2Flox_01flox
SA226665FIT2Flox_02flox
SA226666FIT2Flox_03flox
SA226667FIT2Flox_04flox
SA226668FIT2Flox_05flox
SA226658FIT2-LKO_03Liver Knockout
SA226659FIT2-LKO_04Liver Knockout
SA226660FIT2-LKO_05Liver Knockout
SA226661FIT2-LKO_06Liver Knockout
SA226662FIT2-LKO_02Liver Knockout
SA226663FIT2-LKO_01Liver Knockout
Showing results 1 to 12 of 12

Collection:

Collection ID:CO002382
Collection Summary:All mice fasted 2 hours prior to sacrifice. Mice were euthanized with isoflurane and tissues were collected.
Sample Type:Liver

Treatment:

Treatment ID:TR002401
Treatment Summary:No treatment

Sample Preparation:

Sampleprep ID:SP002395
Sampleprep Summary:Liver (~100mg) was homogenized in 1 mL of PBS using a Bead Mill Homogenizer (VWR). Lipids were extracted, according to the Folch method.
Processing Storage Conditions:On ice
Extract Storage:-80℃

Combined analysis:

Analysis ID AN003763 AN003764
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Thermo Accucore C30 (250 x 2.1mm,3um) Thermo Accucore C30 (250 x 2.1mm,3um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Area Area

Chromatography:

Chromatography ID:CH002783
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Thermo Accucore C30 (250 x 2.1mm,3um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003506
Analysis ID:AN003763
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Mass spectrometry data analysis was performed using LipidSearch version 4.1 SP (Thermo Fisher Scientific). The results were exported to R-Studio where quality control was performed using pairwise correlations between replicates, a principal component analysis comparing sample groups, as well as retention time plot analysis to verify elution clustering within lipid classes. All identified lipids were included for subsequent analyses if they fulfilled the following LipidSearch-based criteria: 1) reject equal to zero, 2) main grade A OR main grade B AND APvalue<0.01 for at least three replicates, and 3) no missing values across all samples.
Ion Mode:POSITIVE
  
MS ID:MS003507
Analysis ID:AN003764
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Mass spectrometry data analysis was performed using LipidSearch version 4.1 SP (Thermo Fisher Scientific). The results were exported to R-Studio where quality control was performed using pairwise correlations between replicates, a principal component analysis comparing sample groups, as well as retention time plot analysis to verify elution clustering within lipid classes. All identified lipids were included for subsequent analyses if they fulfilled the following LipidSearch-based criteria: 1) reject equal to zero, 2) main grade A OR main grade B AND APvalue<0.01 for at least three replicates, and 3) no missing values across all samples.
Ion Mode:NEGATIVE
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