Summary of Study ST003644

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 PR002254. The data can be accessed directly via it's Project DOI: 10.21228/M88J99 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.

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Study IDST003644
Study TitleMouse epidermal lipidomics
Study SummarySkin-specific double knockout (DKO) of acetyl-CoA synthesizing enzymes, ACLY and ACSS2, induces skin barrier dysfunction and systemic fat loss in mice that can be partially rescued by olive oil supplementation. In this study, lipidomics was performed for epidermis derived from DKO versus wild-type mouse skin with or without olive oil supplementation to examine the changes in epidermal lipid profile in response to limited acetyl-CoA availability and to dietary lipid intervention.
Institute
University of Pennsylvania
DepartmentCancer Biology
LaboratoryWellen
Last NameNguyen
First NamePhuong
Address421 Curie Boulevard, Philadelphia PA 19104 USA
Emailpttnguyen27@gmail.com
Phone2674376821
Submit Date2024-12-15
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-01-13
Release Version1
Phuong Nguyen Phuong Nguyen
https://dx.doi.org/10.21228/M88J99
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002254
Project DOI:doi: 10.21228/M88J99
Project Title:Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis
Project Type:MS quantitative analysis
Project Summary:ATP-citrate lyase (ACLY) generates cytosolic acetyl-CoA for lipid synthesis and is a promising therapeutic target in diseases with altered lipid metabolism. Here, we developed inducible whole-body Acly knockout mice to determine the requirement for ACLY in normal tissue functions, uncovering its crucial role in skin homeostasis. ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; deletion of both Acly and Acss2 from the skin exacerbates skin abnormalities, with differential effects on two major lipid-producing skin compartments. While the epidermis is depleted of barrier lipids, the sebaceous glands increase production of sebum, supplied at least in part by circulating fatty acids and coinciding with adipose lipolysis and fat depletion. Dietary fat supplementation further boosts sebum production and partially rescues both the lipoatrophy and aberrant skin phenotypes. The data establish a critical role for cytosolic acetyl-CoA synthesis in maintaining skin barrier integrity and highlight the skin as a key organ in systemic lipid regulation.
Institute:University of Pennsylvania
Department:Cancer Biology
Laboratory:Wellen
Last Name:Nguyen
First Name:Phuong
Address:421 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA
Email:pttnguyen27@gmail.com
Phone:2674376821
Publications:Nguyen, P. et al Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis

Subject:

Subject ID:SU003774
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Age Or Age Range:10 weeks
Gender:Male and female
Animal Light Cycle:7am-7pm
Animal Feed:Standard chow diet with or without olive oil gavage

Factors:

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

mb_sample_id local_sample_id Sample source Genotype Olive oil gavage
SA397848D276Epidermis KO No
SA397849D274Epidermis KO No
SA397850D272Epidermis KO No
SA397851D270Epidermis KO No
SA397852D269Epidermis KO No
SA397853D267Epidermis KO No
SA397854D266Epidermis KO No
SA397855D360Epidermis KO Yes
SA397856D287Epidermis KO Yes
SA397857D286Epidermis KO Yes
SA397858D284Epidermis KO Yes
SA397859D361Epidermis KO Yes
SA397860D364Epidermis KO Yes
SA397861D271Epidermis WT No
SA397862D265Epidermis WT No
SA397863D275Epidermis WT No
SA397864D273Epidermis WT No
SA397865D359Epidermis WT Yes
SA397866D289Epidermis WT Yes
SA397867D288Epidermis WT Yes
SA397868D362Epidermis WT Yes
SA397869D285Epidermis WT Yes
SA397870D365Epidermis WT Yes
SA397871D371Epidermis WT Yes
SA397880BE-01-inj-02extraction blank for exclusion list in MS NA NA
SA397881BE-02-inj-02extraction blank for exclusion list in MS NA NA
SA397882BE-02extraction blank for exclusion list in MS NA NA
SA397883BE-01extraction blank for exclusion list in MS NA NA
SA397884ISTD-D-02internal standard dry NA NA
SA397885ISTD-D-01internal standard dry NA NA
SA397886ISTD-Ext-02internal standard extracted from water NA NA
SA397887ISTD-Ext-01internal standard extracted from water NA NA
SA397872QC_Pool-04-01Pooled from all 24 samples NA NA
SA397873QC_Pool-01-01Pooled from all 24 samples NA NA
SA397874QC_Pool-04-02Pooled from all 24 samples NA NA
SA397875QC_Pool-01-02Pooled from all 24 samples NA NA
SA397876QC_Pool-02-01Pooled from all 24 samples NA NA
SA397877QC_Pool-02-02Pooled from all 24 samples NA NA
SA397878QC_Pool-03-01Pooled from all 24 samples NA NA
SA397879QC_Pool-03-02Pooled from all 24 samples NA NA
Showing results 1 to 40 of 40

Collection:

Collection ID:CO003767
Collection Summary:Epidermis was isolated from mouse skin with dispase enzyme incubation and flash frozen until processed for lipid extraction
Sample Type:Epidermis
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003783
Treatment Summary:Skin-specific double knockout (DKO) of ACLY and ACSS2 was induced by Tamoxifen injections (first injection was day 0). For the treated mice, olive oil gavage was given at 200uL per day on every other day starting at day 11 and ending at day 19. Epidermal tissue was collected on day 21.
Treatment Compound:Olive oil
Treatment Route:Gavage
Treatment Dose:200 µL

Sample Preparation:

Sampleprep ID:SP003781
Sampleprep Summary:5 mg of frozen epidermis was homogenized in 0.6 mL of ice-cold 80% methanol using green bullet blender tubes (Next Advance NA-GREENR1-RNA) and the Next Advance Bullet Blender Tissue Homogenizer with dry ice at max speed x3 for 5 minutes each. The tubes were vortexed and allowed to settle and come to room temp for 30 minutes. 125 µL of homogenate (equivalent to 1 mg of tissue) was transferred into a 10 mL Pyrex Glass tube, followed by adding 20 µL of internal standard mix (1:1, SPLASH® LIPIDOMIX mass spec standard #330707: Ceramide/Sphingoid mixture I #LM6002, both from Avanti Polar Lipids), 80% methanol up to 2 mL of total methanol, and 1.7 mL of chloroform. The mixture was then shaken vigorously for 20 minutes at room temperature. Each sample was added with 1.4 mL of deionized water, vortexed for 30 seconds, and centrifuged at 2000 rpm for 10 minutes for phase separation. The bottom chloroform layer was collected and dried down under nitrogen gas. Then, dried lipids were resuspended in 200 µL of methyl tert-butyl ether:methanol (1:3, v/v), sonicated for 5 minutes in water bath at room temperature, and centrifuged at 10,000 g for 10 minutes at 4°C. A pooled sample was made by mixing 40 µL from each re-dissolved sample. This pooled sample was used as quality control (QC) for the LC-HRMS response and ran every 8 samples. The QC was used for data normalization. The rest of the lipid re-dissolved sample was transferred to a HPLC vial and 2 µL injections were made in both positive mode and separately in the negative mode. Control extraction blanks were made using only solvents instead of the tissue homogenate. The control extraction blanks were used for the exclusion list with a threshold feature intensity set at 1e105.
Processing Storage Conditions:Described in summary
Extract Storage:Described in summary

Chromatography:

Chromatography ID:CH004545
Instrument Name:Ultimate 3000 UPLC system
Column Name:Thermo Accucore C18 (150 x 2.1mm,2.6um)
Column Temperature:35℃
Flow Gradient:0 min, 90% A; 1 min, 90% A; 4 min, 60% A; 12 min, 25% A; 21 min, 1% A; 24 min, 1% A; 24.1 min, 90% A; and 28 min, 90% A
Flow Rate:0.4 mL/min
Solvent A:50% Acetonitrile/50% Water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:10% Acetonitrile/88% Isopropanol/2% Water; 0.02% formic acid; 2 mM ammonium formate
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005983
Analysis Type:MS
Chromatography ID:CH004545
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003644_AN005983_Results.txt
Units:Area under the curve
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