In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Authors
Jung, Su MyungDoxsey, Will G.
Le, Johnny
Haley, John A.
Mazuecos, Lorena
Luciano, Amelia K.
Li, Huawei
Jang, Cholsoon
Guertin, David A.
Document Type
Journal ArticlePublication Date
2021-07-27Keywords
BATbrown adipocyte
brown adipose tissue
brown fat
glucose metabolism
lipid metabolism
metabolomics
stable isotope tracing
temperature acclimation
thermogenesis
Biochemical Phenomena, Metabolism, and Nutrition
Cellular and Molecular Physiology
Lipids
Molecular Biology
Metadata
Show full item recordAbstract
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.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
DOI
10.1016/j.celrep.2021.109459Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42023PubMed ID
34320357Related Resources
Rights
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/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2021.109459
Scopus Count
Except where otherwise noted, this item's license is described as 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/).