Summary of Study ST003009
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.
Study ID | ST003009 |
Study Title | Media_15N BCAA tracing in brown adipocyte |
Study Summary | To determine the metabolic fate and nitrogen flux of BCAA in mouse brown adipocytes, we used 15N labeled BCAA tracing (Leu (NLM-142-1, CIL), Ile (NLM-292-0.25, CIL) and Val (NLM-316-0.5, CIL)) followed by LC-MS analysis. |
Institute | Harvard Medical School |
Last Name | Wang |
First Name | Dandan |
Address | 3 Blackfan Circle |
dandanwang2022@gmail.com | |
Phone | 5083733714 |
Submit Date | 2023-12-13 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2024-02-19 |
Release Version | 1 |
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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 |