Summary of project PR001873
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
| 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 |
Summary of all studies in project PR001873
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003004 | Extracellular fluid metabolomics of BAT and eWAT | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 10 | Uploaded data (559.9M)* |
| ST003005 | Brown fat metabolomics of Chow and HFD diet | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 12 | Uploaded data (661.1M)* |
| ST003006 | BAT metabolomics from cold and TN mouse models | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 19 | Uploaded data (687.2M)* |
| ST003007 | 15N BCAA tracing in brown adipocyte | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 24 | Uploaded data (1.2G)* |
| ST003008 | 13C BCAA tracing in differentiated brown adipocyte | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 18 | Uploaded data (1.1G)* |
| ST003009 | Media_15N BCAA tracing in brown adipocyte | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 24 | Uploaded data (1.1G)* |
| ST003010 | Media_13C BCAA tracing in differentiated brown adipocyte | Mus musculus | Harvard Medical School | MS* | 2024-02-19 | 1 | 9 | Uploaded data (666.9M)* |
