Transcriptome profiling of brown adipose tissue during cold exposure reveals

25 26 We applied digital gene expression profiling to determine the transcriptome of brown and white adipose 27 tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold 28 for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism 29 and pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol30 3-phosphate dehydrogenase 1 (Gpd1) expression was induced in BAT from cold-challenged mice, 31 suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases 32 was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at 33 significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only 34 a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression 35 during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) 36 fluxes through glycolysis and pentose phosphate pathway are induced, the latter providing reducing 37 equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating 38 triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are 39 increased; 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by Pdk2 and Pdk4. In 40 summary, our results demonstrate extensive and diverse gene expression changes related to glucose 41 handling in activated BAT. 42 43