A survey of genes differentially expressed in the brown adipose tissue (BAT) of mice exposed to a range of environmental temperatures was carried out to identify novel genes and pathways associated with the transition of this tissue toward an amplified thermogenic state. The current report focuses on an analysis of the expression patterns of 50 metabolic genes in BAT under control conditions (22 degrees C), cold exposure (4 degrees C, 1 to 48 h), warm acclimation (33 degrees C, 3 wk), or food restriction/meal feeding (animals fed the same amount as warm mice). In general, expression of genes encoding proteins involving glucose uptake and catabolism was significantly elevated in the BAT of cold-exposed mice. The levels of mRNAs encoding proteins critical to de novo lipogenesis were also increased. Gene expression for enzymes associated with procurement and combustion of long chain fatty acids (LCFAs) was increased in the cold. Thus, a model was proposed in which coordinated activation of glucose uptake, fatty acid synthesis, and fatty acid combustion occurs as part of the adaptive thermogenic processes in BAT. Confirmation emerged from in vivo assessments of cold-induced changes in BAT 2-deoxyglucose uptake (increased 2.7-fold), BAT lipogenesis (2.8-fold higher), and incorporation of LCFA carboxyl-carbon into BAT water-soluble metabolites (elevated approximately twofold). It is proposed that temperature-sensitive regulation of distinct intracellular malonyl-CoA pool sizes plays an important role in driving this unique metabolic profile via maintenance of the lipogenic pool but diminution of the carnitine palmitoyltransferase 1 inhibitory pool under cold conditions.