Summary of project PR001476

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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

Summary of all studies in project PR001476

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002303 Fitm2 is required for ER homeostasis and normal function of murine liver Mus musculus Harvard School of Public Health MS 2022-10-26 1 12 Uploaded data (8G)*