Regulatory networks determining substrate utilization in brown adipocytes

Brown adipose tissue (BAT) is often considered as a sink for nutrients to generate heat. However, when the complex hormonal and nervous inputs and intracellular signaling networks regulating substrate utilization are considered, BAT appears much more as a tightly controlled rheostat, regulating body temperature and balancing circulating nutrient levels. Here we provide an overview of key regulatory circuits, including the diurnal rhythm, determining glucose, fatty acid, and amino acid utilization and the interdependency of these nutrients in thermogenesis. Moreover, we discuss additional factors mediating sympathetic BAT activation beyond β-adrenergic signaling and the limitations of glucose-based BAT activity measurements to foster a better understanding and interpretation of BAT activity data.