Summary of Study ST003004

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 PR001873. The data can be accessed directly via it's Project DOI: 10.21228/M8MF0Z 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 IDST003004
Study TitleExtracellular fluid metabolomics of BAT and eWAT
Study SummaryWe quantified metabolites of extracellular fluid samples from BAT and eWAT. Briefly, we collected the BAT_EF samples and eWAT_EF samples from 12 weeks chow diet C57BL/6J mice (n=5). We run the EF metabolomics using high ph HILIC method on Exploris 240.
Institute
Harvard Medical School
Last NameWang
First NameDandan
Address3 Blackfan Circle, Boston, MA, 02115, USA
Emaildandanwang2022@gmail.com
Phone5083733714
Submit Date2023-12-12
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-02-19
Release Version1
Dandan Wang Dandan Wang
https://dx.doi.org/10.21228/M8MF0Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001873
Project DOI:doi: 10.21228/M8MF0Z
Project Title:Uncoupling Metabolic Health from Thermogenesis via BCAA Flux in Brown Fat
Project Type:MS quantitative analysis
Project Summary:Brown adipose tissue (BAT) is best known for thermogenesis. Whereas numerous studies in rodents found tight associations between the metabolic benefits of BAT and enhanced whole-body energy expenditure, emerging evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The underlying mechanism for this dissociation remained unclear. Here, we report that impaired mitochondrial flux of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, encoded by Slc25a44), was sufficient to cause systemic insulin resistance without affecting whole-body energy expenditure or body-weight. We found that brown adipocytes catabolized BCAAs in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, N-acetylated amino acids, and one of the products, glutathione. BAT-selective impairment in mitochondrial BCAA flux led to elevated oxidative stress and insulin resistance in the liver, accompanied by reduced levels of BCAA-derived metabolites in the circulation. In turn, supplementation of glutathione restored insulin sensitivity of BAT-specific MBC knockout mice. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-nitrogen derived metabolites in the BAT, while cold-induced BAT activity is coupled with an active synthesis of these metabolites. Together, the present work uncovers a mechanism through which brown fat controls metabolic health independent of thermogenesis via BCAA-derived nitrogen carriers acting on the liver.
Institute:Harvard Medical School
Last Name:Wang
First Name:Dandan
Address:3 Blackfan Circle, Boston, MA, 02115, USA
Email:dandanwang2022@gmail.com
Phone:5083733714

Subject:

Subject ID:SU003118
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6J
Age Or Age Range:12 weeks
Weight Or Weight Range:25-30g
Gender:Male

Factors:

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

mb_sample_id local_sample_id Tissue
SA326841EF_BAT_neg_1BAT
SA326842EF_BAT_neg_5BAT
SA326843EF_BAT_neg_4BAT
SA326844EF_BAT_neg_2BAT
SA326845EF_BAT_neg_3BAT
SA326846EF_eWAT_neg_5eWAT
SA326847EF_eWAT_neg_4eWAT
SA326848EF_eWAT_neg_1eWAT
SA326849EF_eWAT_neg_2eWAT
SA326850EF_eWAT_neg_3eWAT
Showing results 1 to 10 of 10

Collection:

Collection ID:CO003111
Collection Summary:Animals were sacrificed immediately by cervical dislocation and tissues were rapidly extracted. Tissues were subjected to centrifugation (10 min, 800 g, 4°C) following placement in a 20 μm nylon mesh filter (EMD Millipore).
Sample Type:Extracellular fluid

Treatment:

Treatment ID:TR003127
Treatment Summary:All mice were housed under a 12 h – 12 h light/dark cycle. Room-temperature mice were housed at 23˚C in ventilated cages with an ACH of 25. Mice were fed a standard diet (Lab Diet 5008) and had free access to food and water.

Sample Preparation:

Sampleprep ID:SP003124
Sampleprep Summary:Animals were sacrificed immediately by cervical dislocation. Tissues were subjected to centrifugation (10 min, 800 g, 4°C) following placement in a 20 μm nylon mesh filter (EMD Millipore). Metabolites were extracted by adding extraction buffer at a ratio of 1:100 interstitial fluid to methanol. Samples were then centrifuged twice (5 min, 10,000 g, 4°C) and supernatant was collected.

Combined analysis:

Analysis ID AN004935
Analysis type MS
Chromatography type HILIC
Chromatography system Thermo Vanquish
Column Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo orbitrap exploris 240
Ion Mode NEGATIVE
Units Peak area

Chromatography:

Chromatography ID:CH003724
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
Column Temperature:25 °C
Flow Gradient:The linear gradient eluted from 95% B (0.0–1 min), 95% B to 65% B (1–7.0 min), 65% B to 40% B (7.0–8.0 min), 40% B (8.0–9.0 min), 40% B to 95% B (9.0–9.1 min), then stayed at 95% B for 5.9 min.
Flow Rate:0.4 mL/min
Solvent A:100% water; 25mM ammonium acetate; 25mM ammonium hydroxide
Solvent B:100% acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS004678
Analysis ID:AN004935
Instrument Name:Thermo orbitrap exploris 240
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:ESI source parameters were set as follows: spray voltage, 3500 V or −2800 V, in positive or negative modes, respectively; vaporizer temperature, 350 °C; sheath gas, 50 arb; aux gas, 10 arb; ion transfer tube temperature, 325 °C. The full scan was set as: orbitrap resolution, 60,000; maximum injection time, 100 ms; scan range, 70–1050 Da. The ddMS2 scan was set as: orbitrap resolution, 30,000; maximum injection time, 60 ms; top N setting, 6; isolation width, 1.0 m/z; HCD collision energy (%), 30; Dynamic exclusion mode was set as auto. The data was analyzed by Compound Discoverer 3.3.
Ion Mode:NEGATIVE
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