Summary of Study ST003987
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.
| Study ID | ST003987 |
| Study Title | Glucose-activated JMJD1A drives visceral adipogenesis via α-ketoglutarate-dependent chromatin remodeling (Study part 6 of 6) |
| Study Summary | Understanding how extracellular glucose regulates adipose tissue remodeling is key to decoding metabolic health. Here, we show that the |
| Institute | Tohoku University |
| Last Name | Sakai |
| First Name | Juro |
| Address | 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan |
| juro.sakai.b6@tohoku.ac.jp | |
| Phone | +81-22-717-8117 |
| Submit Date | 2025-06-11 |
| Study Comments | Figure S1I |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d, mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-07-07 |
| Release Version | 1 |
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: | SU004124 |
| 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 |
|---|---|---|---|
| SA454697 | 3T3-L1_0h | 3T3-L1 | 13C6-Glucose |
| SA454698 | 3T3-L1_1h | 3T3-L1 | 13C6-Glucose |
| SA454699 | 3T3-L1_2h | 3T3-L1 | 13C6-Glucose |
| SA454700 | 3T3-L1_4h | 3T3-L1 | 13C6-Glucose |
| Showing results 1 to 4 of 4 |
Collection:
| Collection ID: | CO004117 |
| 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 4ºC. The upper aqueous layer (400 µL) was filtered through a 5 kDa cutoff filter (Millipore), and the filtrate was stored at -80ºC until analysis. At the time 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: | TR004133 |
| Treatment Summary: | 3T3-L1 preadipocytes were differentiated with MDI mixture until day 4 and treated with 25 mM 13C glucose. |
Sample Preparation:
| Sampleprep ID: | SP004130 |
| Sampleprep Summary: | 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. After centrifuge at 10,000xg for 3 min at 4°C, the upper 400 µL water layer was used for CE-MS analysis and 600 µL of methanol containing 2 µM reserpine was added to the remaining chloroform layer and vortex for 10 min. After centrifuge at 10,000xg for 20 min at 4°C again, the supernatant was transferred to a sample vial for LC-MS measurement. |
Chromatography:
| Chromatography ID: | CH004985 |
| Instrument Name: | Agilent 1290 Infinity |
| Column Name: | Waters ACQUITY UPLC HSS T3 (50 x 2.1 mm, 1.8 µm) |
| Column Temperature: | 45℃ |
| Flow Gradient: | 0.0 min 0 % B, 5.0 min 40% B, 7.5-12.0 min 64% B, 12.5 min 82.5% B, 19.0 min 85 % B, 20.0 min 95% B |
| Flow Rate: | 0.3 mL/min |
| Solvent A: | 60% Water/20% Methanol/20% Acetonitrile; 5 mM Ammonium Formate |
| Solvent B: | 100% 2-propanol; 5 mM Ammonium Formate |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006568 |
| Analysis Type: | MS |
| Chromatography ID: | CH004985 |
| Num Factors: | 1 |
| Num Metabolites: | 85 |
| Rt Units: | Minutes |
| Units: | Relative Area |
