Summary of Study ST003063
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 PR001909. The data can be accessed directly via it's Project DOI: 10.21228/M8ZH95 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 | ST003063 |
| Study Title | Uncoupling Metabolic Health from Thermogenesis via BCAA Nitrogen Flux in Brown Fat - Serum metabolomics from control and MBC UCP1-KO |
| Study Summary | Targeted metabolomics in serum from high-fat diet fed control and MBCUCP1 KO mice. N = 6 for control and 7 for MBCUCP1 KO. Statistic: unpaired t-test. Data represented as z-score heatmap with each cell representing quantitated value for each mouse. |
| Institute | BIDMC |
| Last Name | Wang |
| First Name | Dandan |
| Address | 3 Blackfan Circle, Boston, MA, 02115, USA |
| dandanwang2022@gmail.com | |
| Phone | 5083733714 |
| Submit Date | 2024-01-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-19 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001909 |
| Project DOI: | doi: 10.21228/M8ZH95 |
| Project Title: | Uncoupling Metabolic Health from Thermogenesis via BCAA Nitrogen Flux in Brown Fat - Serum metabolomics from control and MBC UCP1-KO |
| Project Summary: | Brown adipose tissue (BAT) is best known for its role in thermogenesis. While many studies in rodents have shown tight associations between the metabolic benefits of BAT and increased whole-body energy expenditure, recent evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, SLC25A44), sufficiently attenuated insulin sensitivity without affecting whole-body energy expenditure and body-weight. We found that brown adipocytes catabolized BCAA in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, alanine, N-acetyl amino acids, and one of the products, glutathione. On the other hand, the contribution of BCAA as a carbon source to the TCA cycle was incremental. Impairment of mitochondrial BCAA nitrogen flux in BAT resulted in increased oxidative stress and decreased insulin signaling in the liver, as well as decreased levels of BCAA-nitrogen derived metabolites in circulation. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-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 regulates metabolic health via BCAA-derived nitrogen carriers that act on the liver, independent of thermogenesis. |
| Institute: | BIDMC |
| Last Name: | Wang |
| First Name: | Dandan |
| Address: | 3 Blackfan Circle, Boston, MA, 02115, USA |
| Email: | dandanwang2022@gmail.com |
| Phone: | 5083733714 |
Subject:
| Subject ID: | SU003178 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA331960 | serum-Con-1 | Control |
| SA331961 | serum-Con-6 | Control |
| SA331962 | serum-Con-5 | Control |
| SA331963 | serum-Con-2 | Control |
| SA331964 | serum-Con-3 | Control |
| SA331965 | serum-Con-4 | Control |
| SA331966 | serum-KO-6 | MBC UCP1-KO |
| SA331967 | serum-KO-7 | MBC UCP1-KO |
| SA331968 | serum-KO-5 | MBC UCP1-KO |
| SA331969 | serum-KO-1 | MBC UCP1-KO |
| SA331970 | serum-KO-2 | MBC UCP1-KO |
| SA331971 | serum-KO-3 | MBC UCP1-KO |
| SA331972 | serum-KO-4 | MBC UCP1-KO |
| Showing results 1 to 13 of 13 |
Collection:
| Collection ID: | CO003171 |
| Collection Summary: | Approximately 20 μL of blood was collected from the tail into tubes containing clotting activator (Starstedt Inc, 16.440.100). The blood samples were kept on ice and the serum was separated by centrifugation at 3,000 g for 10 min at 4 ˚C. |
| Sample Type: | Blood (serum) |
Treatment:
| Treatment ID: | TR003187 |
| Treatment Summary: | No treatment. All animal experiments conducted were performed in compliance of protocols approved by the Institutional Animal Care and Use Committee at Beth Israel Deaconess Medical Center (028-2022). 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. |
Sample Preparation:
| Sampleprep ID: | SP003184 |
| Sampleprep Summary: | Serum metabolites were extracted using a 1:4 ratio of plasma to methanol extraction buffer. After centrifugation at 16,000 g for 15 minutes at 4°C, the supernatant was collected for LC-MS analysis. |
Combined analysis:
| Analysis ID | AN005018 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Agilent 1260 Infinity HPLC |
| Column | Waters Atlantis Silica HILIC (150 x 2.1mm, 3um) |
| MS Type | ESI |
| MS instrument type | QTRAP |
| MS instrument name | ABI Sciex 4000 QTrap |
| Ion Mode | POSITIVE |
| Units | Peak area |
Chromatography:
| Chromatography ID: | CH003791 |
| Instrument Name: | Agilent 1260 Infinity HPLC |
| Column Name: | Waters Atlantis Silica HILIC (150 x 2.1mm, 3um) |
| Column Temperature: | 25 °C |
| Flow Gradient: | 5% mobile phase A (10 mM ammonium formate and 0.1% formic acid in water) for 0.5 minute followed by a linear gradient to 40% mobile phase B (acetonitrile with 0.1% formic acid) over 10 minutes. |
| Flow Rate: | 250 µL/min |
| Solvent A: | 100% water; 10 mM ammonium formate and 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS004757 |
| Analysis ID: | AN005018 |
| Instrument Name: | ABI Sciex 4000 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | MS analyses are carried out using electrospray ionization in the positive ion mode using scheduled MRM method. Multiquant software (version 3.0.3, Sciex) was used for automatic peak integration followed by manual review of all peaks for quality of integration. |
| Ion Mode: | POSITIVE |
