Summary of project PR002778
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 PR002778. The data can be accessed directly via it's Project DOI: 10.21228/M8K84F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002778 |
| Project DOI: | doi: 10.21228/M8K84F |
| Project Title: | Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice |
| Project Type: | Original research |
| Project Summary: | Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed to be contained in lipid droplets (LDs). While studies have been performed in cell culture and Drosophila models to characterize glial LDs, the roles of microglial LD biogenesis in mammalian tauopathy are unclear. To address this issue, we induced the deletion of diacylglycerol acyltransferases 1 and 2 (DGATs), enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. We observed that microglial DGAT double KO exacerbated neurodegeneration and increased the abundance of brain cholesteryl esters in male PS19 mice. Myeloid cell lipid accumulations appeared to largely localize to endosomes/lysosomes not LDs at baseline, and this was exacerbated upon DGAT KO. Our results suggest that microglial DGAT-dependent TAG/LD biogenesis is adaptive in advanced tauopathy. Most lipid accumulation in brain myeloid cells does not correspond to LDs in this tauopathy model, which has implications for the development of lipid-modulating therapies for neurodegenerative diseases. |
| Institute: | Denali Therapeutics |
| Department: | Omics |
| Last Name: | Suh |
| First Name: | Jung |
| Address: | 161 Oyster Point Blvd. South San Francisco, CA 94080 |
| Email: | suh@dnli.com |
| Phone: | 650-534-4840 |
| Publications: | CELL-REPORTS-D-25-07054 |
| Contributors: | G. Travis Tabor, Alexandra Litvinchuk, Elizabeth W. Sun, Bettina van Lengerich, Sonnet S. Davis, Jung H. Suh, Gilbert Di Paolo,and David M. Holtzman |
Summary of all studies in project PR002778
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004385 | Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice | Mus musculus | Denali Therapeutics | MS | 2025-12-09 | 1 | 86 | Uploaded data (28.3M)* |
