Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

Qin Hao, Rachita Yadav, Astrid L. Basse, Sidsel Petersen, Si B. Sonne, Simon Rasmussen, Qianhua Zhu, Zhike Lu, Jun Wang, Karine Marie Laure Audouze, Ramneek Gupta, Lise Madsen, Karsten Kristiansen, Jacob B. Hansen

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    Abstract

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT.
    Original languageEnglish
    JournalAmerican Journal of Physiology: Endocrinology and Metabolism
    Volume308
    Issue number5
    Pages (from-to)E380-E392
    Number of pages13
    ISSN0193-1849
    DOIs
    Publication statusPublished - 2015

    Cite this

    Hao, Q., Yadav, R., Basse, A. L., Petersen, S., Sonne, S. B., Rasmussen, S., Zhu, Q., Lu, Z., Wang, J., Audouze, K. M. L., Gupta, R., Madsen, L., Kristiansen, K., & Hansen, J. B. (2015). Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism. American Journal of Physiology: Endocrinology and Metabolism, 308(5), E380-E392. https://doi.org/10.1152/ajpendo.00277.2014