In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate.
In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate.
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体内同位素追踪揭示了葡萄糖作为棕色脂肪组织底物的多功能性。
DOI：
10.1016/j.celrep.2021.109459
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发表时间：
2021-07-27
期刊：
影响因子：
8.8
通讯作者：
Guertin DA
中科院分区：
文献类型：
--
作者：
Jung SM;Doxsey WG;Le J;Haley JA;Mazuecos L;Luciano AK;Li H;Jang C;Guertin DA
活性棕色脂肪组织(BAT)消耗大量葡萄糖，但葡萄糖代谢如何支持产热尚不清楚。通过结合转录组学、代谢组学和体内稳定同位素示踪，我们系统地分析了小鼠在急性和慢性冷暴露期间对BAT葡萄糖的利用。代谢产物图谱显示，在冷适应时，蝙蝠的代谢组和转录组发生了广泛的温度依赖变化，发现了意想不到的产热代谢物标志，包括N-乙酰-氨基酸的增加。时间-过程稳定同位素示踪进一步揭示了糖酵解和TCA循环中葡萄糖碳的快速结合，以及几个辅助途径，包括NADPH、核苷酸和磷脂合成途径。基因表达差异不一致地预测葡萄糖通量，表明转录后机制也控制着葡萄糖的利用。令人惊讶的是，BAT会迅速从葡萄糖中产生脂肪酸和酰肉碱，这表明脂肪会迅速合成并立即被氧化。这些数据揭示了BAT葡萄糖利用的多样性，突出了综合组学方法对了解器官新陈代谢的价值。Jung等人通过代谢组学、稳定同位素示踪和转录组数据探索棕色脂肪组织体内葡萄糖的利用。他们在蝙蝠代谢组中发现了广泛的依赖于温度的变化，揭示了葡萄糖利用中产热和多功能性的几个标志，包括从头脂肪和酰肉碱合成的快速耦合。
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. Jung et al. explore brown adipose tissue glucose utilization in vivo by metabolomics, stable isotope tracing, and transcriptomics data. They find extensive temperature-dependent changes in the BAT metabolome revealing several markers of thermogenesis and versatility in glucose utilization, including rapid coupling of de novo lipid and acyl-carnitine synthesis.
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影响因子：
4.6
作者：
Held NM;Kuipers EN;van Weeghel M;van Klinken JB;Denis SW;Lombès M;Wanders RJ;Vaz FM;Rensen PCN;Verhoeven AJ;Boon MR;Houtkooper RH
通讯作者：
Houtkooper RH
影响因子：
9.8
作者：
Arnesen T
通讯作者：
Arnesen T
代谢组学和同位素跟踪。
影响因子：
64.5
作者：
Jang C;Chen L;Rabinowitz JD
通讯作者：
Rabinowitz JD
影响因子：
82.9
作者：
Bartelt A;Widenmaier SB;Schlein C;Johann K;Goncalves RLS;Eguchi K;Fischer AW;Parlakgül G;Snyder NA;Nguyen TB;Bruns OT;Franke D;Bawendi MG;Lynes MD;Leiria LO;Tseng YH;Inouye KE;Arruda AP;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
4.1
作者：
ISLER, D;HILL, HP;MEIER, MK
通讯作者：
MEIER, MK