Brown adipose tissue (BAT) has the unique capacity to regulate energy expenditure by a process called adaptive thermogenesis, which dissipates chemical energy to produce heat. If fully active, the BAT depots of adult humans may burn an amount of energy equivalent to about 4 kg of white adipose tissue (WAT) per year. Needless to say, the identification of BAT in adult humans opens up completely new avenues of therapeutic intervention and offers unique scientific opportunities. This entails a need to better understand the molecular mechanisms that regulate BAT metabolism. This presentation is focused on how BAT, WAT and muscle regulate its uptake and use of substrates for metabolism and how this affects the function of these tissues. These studies have led to identification of transcription factors that regulate cellular glycolysis and substrate preference i.e. glucose or fatty acid uptake and further oxidation.