In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate

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.

Automated summary

This study investigates the utilization of glucose by brown adipose tissue (BAT) in mice during cold exposure using a combination of transcriptomics, metabolomics, and stable isotope tracing. The results show extensive temperature-dependent changes in BAT metabolism and transcriptome, with unexpected metabolite markers of thermogenesis. Additionally, the study reveals rapid incorporation of glucose carbons into various metabolic pathways in BAT, highlighting the versatility of BAT glucose utilization.