UMMS Affiliation

Program in Molecular Medicine; Graduate School of Biomedical Sciences

Publication Date

2021-07-27

Document Type

Article

Disciplines

Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Lipids | Molecular Biology

Abstract

Active brown adipose tissue (BAT) consumes copious amounts of glucose, yet how glucose metabolism supports thermogenesis is unclear. By combining transcriptomics, metabolomics, and stable isotope tracing in vivo, we systematically analyze BAT glucose utilization in mice during acute and chronic cold exposure. Metabolite profiling reveals extensive temperature-dependent changes in the BAT metabolome and transcriptome upon cold adaptation, discovering unexpected metabolite markers of thermogenesis, including increased N-acetyl-amino acid production. Time-course stable isotope tracing further reveals rapid incorporation of glucose carbons into glycolysis and TCA cycle, as well as several auxiliary pathways, including NADPH, nucleotide, and phospholipid synthesis pathways. Gene expression differences inconsistently predict glucose fluxes, indicating that posttranscriptional mechanisms also govern glucose utilization. Surprisingly, BAT swiftly generates fatty acids and acyl-carnitines from glucose, suggesting that lipids are rapidly synthesized and immediately oxidized. These data reveal versatility in BAT glucose utilization, highlighting the value of an integrative-omics approach to understanding organ metabolism.

Keywords

BAT, brown adipocyte, brown adipose tissue, brown fat, glucose metabolism, lipid metabolism, metabolomics, stable isotope tracing, temperature acclimation, thermogenesis

Rights and Permissions

Copyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2021.109459

Source

Jung SM, Doxsey WG, Le J, Haley JA, Mazuecos L, Luciano AK, Li H, Jang C, Guertin DA. In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate. Cell Rep. 2021 Jul 27;36(4):109459. doi: 10.1016/j.celrep.2021.109459. PMID: 34320357; PMCID: PMC8369932. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

34320357

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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