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 |
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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 |
