Summary of Study ST004385

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

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	ST004385
Study Title	Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice
Study Type	Original research
Study 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 H.
Address	161 Oyster Point Blvd. South San Francisco, CA 94080
Email	suh@dnli.com
Phone	650-534-4840
Submit Date	2025-11-18
Num Groups	4
Total Subjects	86
Num Males	40
Num Females	40
Study Comments	There were 6 pooled QC samples in addition to 80 samples
Publications	Cell Reports
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-12-09
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

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

Subject:

Subject ID:	SU004544
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Genotype Strain:	PS19 mice harboring a P301S mutant human 1N4R MAPT transgene driven by the prion promoter were previously acquired from Jackson laboratories (Stock no. 008169) and backcrossed to C57BL/6 mice (Stock no. 027, Charles River) for more than 10 generations.
Age Or Age Range:	9.5 mo
Gender:	Male and female
Animal Animal Supplier:	Jackson

Factors:

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

mb_sample_id	local_sample_id	Sample source	SEX	Genotype	Treatment
SA520461	LSCF563	Brain	Female	PS19	OIL
SA520462	LSCF864	Brain	Female	PS19	OIL
SA520463	LSCF807	Brain	Female	PS19	OIL
SA520464	LSCF681	Brain	Female	PS19	OIL
SA520465	LSCF575	Brain	Female	PS19	OIL
SA520466	LSCF776	Brain	Female	PS19	OIL
SA520467	LSCF675	Brain	Female	PS19	OIL
SA520468	LSCF821	Brain	Female	PS19	OIL
SA520469	LSCF696	Brain	Female	PS19	OIL
SA520470	LSCF602	Brain	Female	PS19	OIL
SA520471	LSDF639	Brain	Female	PS19	TAMOXIFEN
SA520472	LSDF588	Brain	Female	PS19	TAMOXIFEN
SA520473	LSDF680	Brain	Female	PS19	TAMOXIFEN
SA520474	LSDF853	Brain	Female	PS19	TAMOXIFEN
SA520475	LSDF806	Brain	Female	PS19	TAMOXIFEN
SA520476	LSDF708	Brain	Female	PS19	TAMOXIFEN
SA520477	LSDF671	Brain	Female	PS19	TAMOXIFEN
SA520478	LSDF775	Brain	Female	PS19	TAMOXIFEN
SA520479	LSDF842	Brain	Female	PS19	TAMOXIFEN
SA520480	LSDF673	Brain	Female	PS19	TAMOXIFEN
SA520481	LSAF912	Brain	Female	WT	OIL
SA520482	LSAF916	Brain	Female	WT	OIL
SA520483	LSAF883	Brain	Female	WT	OIL
SA520484	LSAF866	Brain	Female	WT	OIL
SA520485	LSAF891	Brain	Female	WT	OIL
SA520486	LSAF883_a	Brain	Female	WT	OIL
SA520487	LSAF872	Brain	Female	WT	OIL
SA520488	LSAF914	Brain	Female	WT	OIL
SA520489	LSAF897	Brain	Female	WT	OIL
SA520490	LSAF899	Brain	Female	WT	OIL
SA520491	LSBF881_a	Brain	Female	WT	TAMOXIFEN
SA520492	LSBF871	Brain	Female	WT	TAMOXIFEN
SA520493	LSBF913	Brain	Female	WT	TAMOXIFEN
SA520494	LSBF898	Brain	Female	WT	TAMOXIFEN
SA520495	LSBF865	Brain	Female	WT	TAMOXIFEN
SA520496	LSBF873	Brain	Female	WT	TAMOXIFEN
SA520497	LSBF915	Brain	Female	WT	TAMOXIFEN
SA520498	LSBF904	Brain	Female	WT	TAMOXIFEN
SA520499	LSBF884_a	Brain	Female	WT	TAMOXIFEN
SA520500	LSBF919	Brain	Female	WT	TAMOXIFEN
SA520501	LSCM597	Brain	Male	PS19	OIL
SA520502	LSCM701	Brain	Male	PS19	OIL
SA520503	LSCM783	Brain	Male	PS19	OIL
SA520504	LSCM612	Brain	Male	PS19	OIL
SA520505	LSCM881	Brain	Male	PS19	OIL
SA520506	LSCM694	Brain	Male	PS19	OIL
SA520507	LSCM880	Brain	Male	PS19	OIL
SA520508	LSCM796b	Brain	Male	PS19	OIL
SA520509	LSCM833	Brain	Male	PS19	OIL
SA520510	LSCM655	Brain	Male	PS19	OIL
SA520511	LSDM859	Brain	Male	PS19	TAMOXIFEN
SA520512	LSDM633	Brain	Male	PS19	TAMOXIFEN
SA520513	LSDM828	Brain	Male	PS19	TAMOXIFEN
SA520514	LSDM527	Brain	Male	PS19	TAMOXIFEN
SA520515	LSDM668	Brain	Male	PS19	TAMOXIFEN
SA520516	LSDM781	Brain	Male	PS19	TAMOXIFEN
SA520517	LSDM641	Brain	Male	PS19	TAMOXIFEN
SA520518	LSDM862	Brain	Male	PS19	TAMOXIFEN
SA520519	LSDM869	Brain	Male	PS19	TAMOXIFEN
SA520520	LSDM780	Brain	Male	PS19	TAMOXIFEN
SA520521	LSAM712	Brain	Male	WT	OIL
SA520522	LSAM667	Brain	Male	WT	OIL
SA520523	LSAM611	Brain	Male	WT	OIL
SA520524	LSAM734	Brain	Male	WT	OIL
SA520525	LSAM784	Brain	Male	WT	OIL
SA520526	LSAM640	Brain	Male	WT	OIL
SA520527	LSAM724	Brain	Male	WT	OIL
SA520528	LSAM782	Brain	Male	WT	OIL
SA520529	LSAM818	Brain	Male	WT	OIL
SA520530	LSAM686	Brain	Male	WT	OIL
SA520531	LSBM800b	Brain	Male	WT	TAMOXIFEN
SA520532	LSBM687	Brain	Male	WT	TAMOXIFEN
SA520533	LSBM674	Brain	Male	WT	TAMOXIFEN
SA520534	LSBM652	Brain	Male	WT	TAMOXIFEN
SA520535	LSBM810	Brain	Male	WT	TAMOXIFEN
SA520536	LSBM771	Brain	Male	WT	TAMOXIFEN
SA520537	LSBM693	Brain	Male	WT	TAMOXIFEN
SA520538	LSBM756	Brain	Male	WT	TAMOXIFEN
SA520539	LSBM713	Brain	Male	WT	TAMOXIFEN
SA520540	LSBM809	Brain	Male	WT	TAMOXIFEN
SA520541	Pool_005	Brain	NA	NA	NA
SA520542	Pool_006	Brain	NA	NA	NA
SA520543	Pool_004	Brain	NA	NA	NA
SA520544	Pool_002	Brain	NA	NA	NA
SA520545	Pool_003	Brain	NA	NA	NA
SA520546	Pool_001	Brain	NA	NA	NA

Showing results 1 to 86 of 86

Showing results 1 to 86 of 86

Collection:

Collection ID:	CO004537
Collection Summary:	Mice were anesthetized by i.p. injection of pentobarbital (Fatal Plus). After the mice became unresponsive to toe pinch, blood was collected from the right ventricle into an EDTA-coated syringe using either 23- or 26-gauge needles (23-gauge needles are preferred). Mice were then transcardially perfused (via the left ventricle) with ~21 mL of 0.3% heparin (Hepalink, NDC 81952-112-05)/PBS at a rate of ~7 mL per minute.The right hemibrain was micro-dissected and hippocampal, cortical, cerebellar, brainstem, thalamus, hypothalamus, and liver specimens were flash frozen and stored at -80C for subsequent lcms analysis.
Sample Type:	Brain cortex

Treatment:

Treatment ID:	TR004553
Treatment Summary:	Male mice were weaned into cages designated for treatment with TAM or OIL to avoid fighting. Females were occasionally consolidated into treatment cages just before the gavage regimen. Tamoxifen (‘TAM,’ Sigma, T5648) was dissolved in corn oil (‘OIL’, Sigma, C8267) at a concentration of 20 mg/mL by shaking at 37C overnight. Aliquots were frozen at -20C and thawed just before use. A given aliquot was stored at 4C between treatment days for up to one month or until precipitation was observed. Mice were gavaged using 20 or 22G bent metal needles. For the male experiments, mice were gavaged with 200 mg/kg TAM (10 µL per gram bodyweight) once per day for 5 days in a row at 3 months of age. For the female experiments, mice were gavaged with the same regimen starting at 6 months of age.

Treatment ID:

TR004553

Treatment Summary:

Male mice were weaned into cages designated for treatment with TAM or OIL to avoid fighting. Females were occasionally consolidated into treatment cages just before the gavage regimen. Tamoxifen (‘TAM,’ Sigma, T5648) was dissolved in corn oil (‘OIL’, Sigma, C8267) at a concentration of 20 mg/mL by shaking at 37C overnight. Aliquots were frozen at -20C and thawed just before use. A given aliquot was stored at 4C between treatment days for up to one month or until precipitation was observed. Mice were gavaged using 20 or 22G bent metal needles. For the male experiments, mice were gavaged with 200 mg/kg TAM (10 µL per gram bodyweight) once per day for 5 days in a row at 3 months of age. For the female experiments, mice were gavaged with the same regimen starting at 6 months of age.

Sample Preparation:

Sampleprep ID:	SP004550
Sampleprep Summary:	Approximately 20 mg of flash-frozen brain tissue was homogenized in 400 μL of methanol extraction buffer containing stable isotope-labeled and surrogate internal standards. Homogenization was carried out using a 3 mm tungsten carbide bead with a Qiagen TissueLyzer II, operating at 25 Hz for 30 seconds, repeated twice. The resulting lysate was centrifuged at 21,000 g for 20 minutes at 4C, and the supernatant was collected. To enhance protein precipitation, the supernatant was stored at - 20C for 1 hour, followed by a second centrifugation at 4,000 g for 20 minutes at 4C. A 200 μL aliquot of the clarified methanol supernatant was subsequently transferred for LC-MS analysis.

Sampleprep ID:

SP004550

Sampleprep Summary:

Approximately 20 mg of flash-frozen brain tissue was homogenized in 400 μL of methanol extraction buffer containing stable isotope-labeled and surrogate internal standards. Homogenization was carried out using a 3 mm tungsten carbide bead with a Qiagen TissueLyzer II, operating at 25 Hz for 30 seconds, repeated twice. The resulting lysate was centrifuged at 21,000 g for 20 minutes at 4C, and the supernatant was collected. To enhance protein precipitation, the supernatant was stored at - 20C for 1 hour, followed by a second centrifugation at 4,000 g for 20 minutes at 4C. A 200 μL aliquot of the clarified methanol supernatant was subsequently transferred for LC-MS analysis.

Combined analysis:

Analysis ID	AN007326	AN007327
Chromatography ID	CH005560	CH005560
MS ID	MS007020	MS007021
Analysis type	MS	MS
Chromatography type	Reversed phase	Reversed phase
Chromatography system	Agilent 1290 Infinity II	Agilent 1290 Infinity II
Column	Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)	Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
MS Type	ESI	ESI
MS instrument type	Triple quadrupole	Triple quadrupole
MS instrument name	ABI Sciex 6500+ QTrap	ABI Sciex 6500+ QTrap
Ion Mode	POSITIVE	NEGATIVE
Units	Peak area	Peak area

Chromatography:

Chromatography ID:	CH005560
Instrument Name:	Agilent 1290 Infinity II
Column Name:	Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:	55
Flow Gradient:	0.0-8.0 min from 45% B to 99% B, 8.0-9.0 min at 99% B, 9.0-9.1 min to 45% B, and 9.1-10.0 min at 45% B
Flow Rate:	0.25 mL/min
Solvent A:	60% acetonitrile/40% water; 10 mM ammonium acetate; 0.1% acetic acid
Solvent B:	90% isopropyl alcohol/10% acetonitrile; 10 mM ammonium acetate; 0.1% acetic acid
Chromatography Type:	Reversed phase

MS:

MS ID:	MS007020
Analysis ID:	AN007326
Instrument Name:	ABI Sciex 6500+ QTrap
Instrument Type:	Triple quadrupole
MS Type:	ESI
MS Comments:	curtain gas at 30 psi; collision gas was set at medium; ion spray voltage at 5,500 V; temperature at 600°C; ion source Gas 1 at 50 psi; ion source Gas 2 at 60 psi
Ion Mode:	POSITIVE

MS ID:	MS007021
Analysis ID:	AN007327
Instrument Name:	ABI Sciex 6500+ QTrap
Instrument Type:	Triple quadrupole
MS Type:	ESI
MS Comments:	curtain gas at 30 psi; collision gas set at medium; ion spray voltage at 4,500 V; temperature at 600°C; ion source Gas 1 at 55 psi; ion source Gas 2 at 60 psi.
Ion Mode:	NEGATIVE