Summary of Study ST003923

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 PR002456. The data can be accessed directly via it's Project DOI: 10.21228/M85R9F 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 IDST003923
Study TitleSex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid synthesis in mice
Study SummaryBrown adipose tissue (BAT), a thermogenic tissue that plays an important role in systemic energy expenditure, has histological and functional sex differences. BAT thermogenic activity is higher in female mice than in male mice. However, the molecular mechanism underlying this functional sex difference has not been fully elucidated. Herein, we demonstrate the role and mechanism of PGC-1α in this sex difference. Inducible adipocyte-specific PGC-1α knockout (KO) mice display mitochondrial morphological defects and decreased BAT thermogenesis only in females. Expression of carbohydrate response-element binding protein beta (Chrebpβ) and its downstream de novo lipogenesis (DNL)-related genes are both reduced only in female KO mice. BAT-specific knockdown of ChREBPβ displays decreased DNL-related gene expression and mitochondrial morphological defects followed by reduced BAT thermogenesis in female wild-type mice. Lipidomics reveals that, PGC-1α increases ether-linked phosphatidylethanolamine (PE) and cardiolipin(18:2)₄ levels through Chrebpβ-dependent and -independent mechanisms in female BAT. Furthermore, PGC-1α enhances the sensitivity of female BAT estrogen signaling, thereby increasing Chrebpβ and its downstream DNL-related gene expression. These findings demonstrate that PGC-1α–mediated phospholipid synthesis plays a pivotal role in BAT thermogenesis in a sex-dependent manner.
Institute
Institute of Science Tokyo
Last NameTsujimoto
First NameKazutaka
Address1-5-45 Yushima, Bunkyo-ku, Tokyo, Tokyo, 113-8510, Japan
Emailktsumem@tmd.ac.jp
Phone+81-3-5803-5216
Submit Date2025-05-07
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailCE-MS
Release Date2025-06-09
Release Version1
Kazutaka Tsujimoto Kazutaka Tsujimoto
https://dx.doi.org/10.21228/M85R9F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002456
Project DOI:doi: 10.21228/M85R9F
Project Title:Sex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid synthesis in mice
Project Summary:Brown adipose tissue (BAT), a thermogenic tissue that plays an important role in systemic energy expenditure, has histological and functional sex differences. BAT thermogenic activity is higher in female mice than in male mice. However, the molecular mechanism underlying this functional sex difference has not been fully elucidated. Herein, we demonstrate the role and mechanism of PGC-1α in this sex difference. Inducible adipocyte-specific PGC-1α knockout (KO) mice display mitochondrial morphological defects and decreased BAT thermogenesis only in females. Expression of carbohydrate response-element binding protein beta (Chrebpβ) and its downstream de novo lipogenesis (DNL)-related genes are both reduced only in female KO mice. BAT-specific knockdown of ChREBPβ displays decreased DNL-related gene expression and mitochondrial morphological defects followed by reduced BAT thermogenesis in female wild-type mice. Lipidomics reveals that, PGC-1α increases ether-linked phosphatidylethanolamine (PE) and cardiolipin(18:2)₄ levels through Chrebpβ-dependent and -independent mechanisms in female BAT. Furthermore, PGC-1α enhances the sensitivity of female BAT estrogen signaling, thereby increasing Chrebpβ and its downstream DNL-related gene expression. These findings demonstrate that PGC-1α–mediated phospholipid synthesis plays a pivotal role in BAT thermogenesis in a sex-dependent manner.
Institute:Institute of Science Tokyo
Last Name:Tsujimoto
First Name:Kazutaka
Address:1-5-45 Yushima, Bunkyo-ku, Tokyo, Tokyo, 113-8510, Japan
Email:ktsumem@tmd.ac.jp
Phone:+81-3-5803-5216

Subject:

Subject ID:SU004058
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male and female

Factors:

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

mb_sample_id local_sample_id Sample source Sex Genotype
SA444333F2BAT Female Control
SA444334F5BAT Female Control
SA444335F4BAT Female Control
SA444336F3BAT Female Control
SA444337F1BAT Female Control
SA444338FC2BAT Female KO
SA444339FC1BAT Female KO
SA444340FC3BAT Female KO
SA444341FC4BAT Female KO
SA444342FC5BAT Female KO
SA444343M5BAT Male Control
SA444344M2BAT Male Control
SA444345M4BAT Male Control
SA444346M3BAT Male Control
SA444347M1BAT Male Control
SA444348MC2BAT Male KO
SA444349MC3BAT Male KO
SA444350MC4BAT Male KO
SA444351MC5BAT Male KO
SA444352MC1BAT Male KO
Showing results 1 to 20 of 20

Collection:

Collection ID:CO004051
Collection Summary:All mice were treated with norepinephrine (NE) and exposed to a warm environment (33°C) for 30 minutes prior to tissue collection, to evaluate brown adipose tissue (BAT) metabolism under conditions of maximal oxygen consumption. Tissues were collected from mice following euthanasia. Brown adipose tissue was isolated and immediately frozen in liquid nitrogen before being stored at -80°C for later analysis.
Sample Type:Brown adipose tissue

Treatment:

Treatment ID:TR004067
Treatment Summary:Tamoxifen-inducible adipocyte-specific PGC-1α knockout (KO) mice were generated by crossing Pgc1a flox/flox mice (JAX stock #009666) with Adipoq-CreERT2 mice (JAX stock #025124). Eight-week-old male and female KO and floxed Control mice were injected intraperitoneally with tamoxifen (100 mg/kg) for 5 consecutive days and analyzed at least 8 weeks after the last injection. All mice were maintained at 30°C for one week before NE injection and tissue sampling. At the time of sacrifice, mice were placed at 33°C and injected with norepinephrine (NE, 1 mg/kg, i.p.). Thirty minutes after NE administration, brown adipose tissue (BAT) was collected for metabolomic analysis.

Sample Preparation:

Sampleprep ID:SP004064
Sampleprep Summary:Approximately 25–30 mg of frozen BAT was homogenized with zirconia beads in 50% acetonitrile containing internal standards. After centrifugation, the aqueous layer was filtered through a 5-kDa cutoff filter, dried under vacuum, and reconstituted in Milli-Q water for metabolomic analysis.

Combined analysis:

Analysis ID AN006440 AN006441
Analysis type MS MS
Chromatography type CE CE
Chromatography system Agilent 7100 CE Agilent 7100 CE
Column Agilent Fused silica capillary (80cm x 50um) Agilent Fused silica capillary (80cm x 50um)
MS Type ESI ESI
MS instrument type TOF TOF
MS instrument name Agilent 6230 TOF Agilent 6230 TOF
Ion Mode POSITIVE NEGATIVE
Units arbitrary unit arbitrary unit

Chromatography:

Chromatography ID:CH004887
Chromatography Summary:Fused silica capillary (50 μm i.d. × 80 cm). H3301-1001 (for cation analysis) and H3302-1021 (for anion analysis) are commercial electrophoresis buffers provided by Human Metabolome Technologies (HMT). H3301-1001 is optimized for the separation of cationic metabolites such as amino acids and polyamines, typically under slightly acidic conditions. H3302-1021 is designed for the separation of anionic metabolites such as organic acids and phosphorylated compounds, under basic conditions.
Instrument Name:Agilent 7100 CE
Column Name:Agilent Fused silica capillary (80cm x 50um)
Column Temperature:N/A
Flow Gradient:N/A
Flow Rate:N/A
Solvent A:HMT electrophoresis buffer H3301-1001
Solvent B:N/A
Chromatography Type:CE
  
Chromatography ID:CH004888
Chromatography Summary:Fused silica capillary (50 μm i.d. × 80 cm). H3302-1021 is designed for the separation of anionic metabolites such as organic acids and phosphorylated compounds, under basic conditions.
Instrument Name:Agilent 7100 CE
Column Name:Agilent Fused silica capillary (80cm x 50um)
Column Temperature:N/A
Flow Gradient:N/A
Flow Rate:N/A
Solvent A:HMT electrophoresis buffer H3302-1021
Solvent B:N/A
Chromatography Type:CE

MS:

MS ID:MS006140
Analysis ID:AN006440
Instrument Name:Agilent 6230 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:CE-TOFMS in positive ion mode (m/z 50–1000). Peaks extracted using MasterHands and MassHunter (Agilent) and annotated based on m/z and migration time using HMT metabolite database.
Ion Mode:POSITIVE
  
MS ID:MS006141
Analysis ID:AN006441
Instrument Name:Agilent 6230 TOF
Instrument Type:TOF
MS Type:ESI
MS Comments:CE-MS/MS in negative ion mode using dynamic MRM. Peaks extracted using MasterHands and MassHunter (Agilent) and annotated based on m/z and migration time using HMT metabolite database.
Ion Mode:NEGATIVE
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