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

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Treatment:

Treatment ID:TR002401
Treatment Summary:No treatment
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