Summary of Study ST003976

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 PR002491. The data can be accessed directly via it's Project DOI: 10.21228/M8NN8C 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 IDST003976
Study TitleGlucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling (Study part 6 of 1)
Study SummaryUnderstanding how extracellular glucose regulates adipose tissue remodeling is key to decoding metabolic health. Here, we show that the histone demethylase JMJD1A senses glucose availability via α-ketoglutarate (α-KG), a TCA cycle metabolite derived from glycolysis. Upon glucose stimulation, α-KG accumulates in the nucleus and activates JMJD1A to remove repressive H3K9me2 marks at glycolytic and adipogenic gene loci, including Pparg. This initiates a transcriptional feedforward loop that amplifies glycolysis and de novo adipogenesis. Mechanistically, JMJD1A is pre-recruited to chromatin by NFIC, and glucose-induced demethylation enables subsequent ChREBP binding. In vivo, mice lacking JMJD1A in adipocyte precursors exhibit impaired adipose tissue hyperplasia and compensatory hypertrophic expansion selectively in visceral fat, resulting in metabolically unfavorable remodeling. These findings uncover a glucose-sensing α-KG-JMJD1A pathway that regulates histone demethylation and de novo adipogenesis, enabling adaptive expansion of visceral adipose tissue under nutrient excess conditions.
Institute
Tohoku University
Last NameSakai
First NameJuro
Address2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
Emailjuro.sakai.b6@tohoku.ac.jp
Phone+81-22-717-8117
Submit Date2025-06-11
Study CommentsFigure 1C, 1D, S1F
Raw Data AvailableYes
Raw Data File Type(s)d, mzML
Analysis Type DetailCE-MS
Release Date2025-07-07
Release Version1
Juro Sakai Juro Sakai
https://dx.doi.org/10.21228/M8NN8C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002491
Project DOI:doi: 10.21228/M8NN8C
Project Title:Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling
Project Summary:Understanding how extracellular glucose regulates adipose tissue remodeling is key to decoding metabolic health. Here, we show that the histone demethylase JMJD1A senses glucose availability via α-ketoglutarate (α-KG), a TCA cycle metabolite derived from glycolysis. Upon glucose stimulation, α-KG accumulates in the nucleus and activates JMJD1A to remove repressive H3K9me2 marks at glycolytic and adipogenic gene loci, including Pparg. This initiates a transcriptional feedforward loop that amplifies glycolysis and de novo adipogenesis. Mechanistically, JMJD1A is pre-recruited to chromatin by NFIC, and glucose-induced demethylation enables subsequent ChREBP binding. In vivo, mice lacking JMJD1A in adipocyte precursors exhibit impaired adipose tissue hyperplasia and compensatory hypertrophic expansion selectively in visceral fat, resulting in metabolically unfavorable remodeling. These findings uncover a glucose-sensing α-KG-JMJD1A pathway that regulates histone demethylation and de novo adipogenesis, enabling adaptive expansion of visceral adipose tissue under nutrient excess conditions.
Institute:Tohoku University
Last Name:Sakai
First Name:Juro
Address:2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
Email:juro.sakai.b6@tohoku.ac.jp
Phone:+81-22-717-8117

Subject:

Subject ID:SU004113
Subject Type:Cultured cells
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Sample source Treatment
SA4542693T3-L1_D0_A3T3-L1 -
SA4542703T3-L1_D0_B3T3-L1 -
SA4542713T3-L1_D0_C3T3-L1 -
SA4542723T3-L1_D2_A3T3-L1 MDI
SA4542733T3-L1_D2_B3T3-L1 MDI
SA4542743T3-L1_D2_C3T3-L1 MDI
SA4542753T3-L1_D4_A3T3-L1 MDI
SA4542763T3-L1_D4_B3T3-L1 MDI
SA4542773T3-L1_D4_C3T3-L1 MDI
SA4542783T3-L1_D6_A3T3-L1 MDI
SA4542793T3-L1_D6_B3T3-L1 MDI
SA4542803T3-L1_D6_C3T3-L1 MDI
SA4542813T3-L1_D8_A3T3-L1 MDI
SA4542823T3-L1_D8_B3T3-L1 MDI
SA4542833T3-L1_D8_C3T3-L1 MDI
Showing results 1 to 15 of 15

Collection:

Collection ID:CO004106
Collection Summary:3T3-L1 cells were washed twice with 5% mannitol before metabolite extraction. Aqueous metabolites were extracted with 400 µL of methanol containing three internal standards (3ISs; methionine sulfone, 2-(N-morpholino)ethanesulfonic acid [MES] and D-camphol-10-sulfonic acid [CSA]; 25 µM each) at room temperature for 10 min. Then 400 µL chloroform and 200 µL of water were added, and the solution was centrifuged at 10,000 × g for 3 min at 4 ºC. The upper aqueous layer (400 µL) was filtered through a 5 kDa cutoff filter (Millipore), and the filtrate was stored at -80 ºC until analysis. At the teime of analysis, the filtrate was thawed and centrifugally concentrated and dissolved in 25 µL of water containing reference compounds (3-aminopyrrolidine and 1,3,5-benzenetricarboxylic acid; 200 µM each).
Sample Type:Cultured cells

Treatment:

Treatment ID:TR004122
Treatment Summary:3T3-L1 preadipocytes were differentiated with MDI (IBMX, dexamethasone, and insulin) mixture.

Sample Preparation:

Sampleprep ID:SP004119
Sampleprep Summary:For metabolite extraction, the 3T3-L1 cells were washed twice with ice-cold 5% mannitol solution and covered with 1 mL of methanol containing 25 µM internal standards for 10 min. 400 µL of the resulting extracts were mixed with 200 µL of Milli-Q water and 400 µL of chloroform. 400 µL of the aqueous solution was centrifugally filtered through a 5-kDa cut-off filter (Human Metabolome Technologies, Tsuruoka, Japan) to remove proteins. The filtrate was centrifugally concentrated and dissolved in 50 µL of Milli-Q water that contained reference compounds (200 µM each of 3-aminopyrrolidine and trimesate) immediately prior to metabolome analysis.

Chromatography:

Chromatography ID:CH004967
Instrument Name:Agilent CE
Column Name:COSMO(+) capillary i. d. 50 µm x 105 cm
Column Temperature:N/A
Flow Gradient:N/A
Flow Rate:N/A
Solvent A:100% water; 50 mM ammonium acetate, pH 8.5
Solvent B:N/A
Chromatography Type:CE
  
Chromatography ID:CH004968
Instrument Name:Agilent CE
Column Name:Fused silica capillary i. d. 50 µm x 100 cm
Column Temperature:N/A
Flow Gradient:N/A
Flow Rate:N/A
Solvent A:100% water; 1 M formic acid
Solvent B:N/A
Chromatography Type:CE

Analysis:

Analysis ID:AN006548
Analysis Type:MS
Chromatography ID:CH004967
Num Factors:2
Num Metabolites:102
Units:fmol/cell
  
Analysis ID:AN006549
Analysis Type:MS
Chromatography ID:CH004968
Num Factors:2
Num Metabolites:105
Units:fmol/cell
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