Summary of Study ST003005

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 IDST003005
Study TitleBrown fat metabolomics of Chow and HFD diet
Study SummaryBrown adipose tissue (BAT) metabolites in mice fed a standard diet or a high-fat diet for 12 weeks. N = 6 per group.
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:SU003119
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 Diet
SA326851BAT_chow_neg_1Chow
SA326852BAT_chow_neg_6Chow
SA326853BAT_chow_neg_5Chow
SA326854BAT_chow_neg_2Chow
SA326855BAT_chow_neg_3Chow
SA326856BAT_chow_neg_4Chow
SA326857BAT_HFD_neg_6HFD
SA326858BAT_HFD_neg_5HFD
SA326859BAT_HFD_neg_1HFD
SA326860BAT_HFD_neg_2HFD
SA326861BAT_HFD_neg_3HFD
SA326862BAT_HFD_neg_4HFD
Showing results 1 to 12 of 12

Collection:

Collection ID:CO003112
Collection Summary:Animals were sacrificed immediately by cervical dislocation and tissues were rapidly extracted and immediately snap frozen in liquid nitrogen for metabolite profiling.
Sample Type:Brown fat tissue

Treatment:

Treatment ID:TR003128
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) or high-fat diet (Research Diets; D12492; 60% Fat) and had free access to food and water.

Sample Preparation:

Sampleprep ID:SP003125
Sampleprep Summary:Animals were sacrificed immediately by cervical dislocation and tissues were rapidly extracted and immediately snap frozen in liquid nitrogen for metabolite profiling. For metabolite extraction, tissues were weighed and then homogenized with extraction buffer which consisted of 80% methanol containing D₈-Phenylalanine internal standards at a 40:1 volume to wet weight ratio. Samples were centrifuged at 16,000 x g at 4 °C for 15 min. Finally, 50 μL supernatant was transferred to the glass insert for LC-MS detection.

Combined analysis:

Analysis ID AN004936
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:CH003725
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:MS004679
Analysis ID:AN004936
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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