Obesity develops when energy intake chronically exceeds energy expenditure. 
Because brown adipose tissue (BAT) dissipates energy in the form of heat, 
increasing energy expenditure by augmenting BAT-mediated thermogenesis may 
represent an approach to counter obesity and its complications. The ability of 
BAT to dissipate energy is dependent on expression of mitochondrial uncoupling 
protein 1 (UCP1). To facilitate the identification of pharmacological modulators 
of BAT UCP1 levels, which may have potential as antiobesity medications, we 
developed a transgenic model in which luciferase activity faithfully mimics 
endogenous UCP1 expression and its response to physiologic stimuli. Phenotypic 
screening of a library using cells derived from this model yielded a small 
molecule that increases UCP1 expression in brown fat cells and mice. Upon 
adrenergic stimulation, compound-treated mice showed increased energy 
expenditure. These tools offer an opportunity to identify pharmacologic 
modulators of UCP1 expression and uncover regulatory pathways that impact 
BAT-mediated thermogenesis.