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.
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 | ST002303 |
Study Title | Fitm2 is required for ER homeostasis and normal function of murine liver |
Study 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 School of Public Health |
Last Name | Bond |
First Name | Laura |
Address | 665 Huntington Ave., Building 2, 3rd Floor, Room 311 | Boston, MA 02115 |
laurabond44@gmail.com | |
Phone | 8573087183 |
Submit Date | 2022-09-17 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2022-10-26 |
Release Version | 1 |
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 |
---|---|---|
SA226657 | Blank | Blank |
SA226664 | FIT2Flox_01 | flox |
SA226665 | FIT2Flox_02 | flox |
SA226666 | FIT2Flox_03 | flox |
SA226667 | FIT2Flox_04 | flox |
SA226668 | FIT2Flox_05 | flox |
SA226658 | FIT2-LKO_03 | Liver Knockout |
SA226659 | FIT2-LKO_04 | Liver Knockout |
SA226660 | FIT2-LKO_05 | Liver Knockout |
SA226661 | FIT2-LKO_06 | Liver Knockout |
SA226662 | FIT2-LKO_02 | Liver Knockout |
SA226663 | FIT2-LKO_01 | Liver 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 |