Renaissance of brown adipose tissue research: integrating the old and new.

The recent demonstration of active brown adipose tissue (BAT) in adult humans, along with the discovery of vast cellular and metabolic plasticity of adipocyte phenotypes, has given new hope of targeting adipose tissue for therapeutic benefit. Application of principles learned from the first wave of obesity-related BAT research, conducted 30 years earlier, suggests that the activity and/or mass of brown fat will need to be greatly expanded for it to significantly contribute to total energy expenditure. Although the thermogenic capacity of human brown fat is very modest, its presence often correlates with improved metabolic status, suggesting possible beneficial endocrine functions. Recent advances in our understanding of the nature of progenitors and the transcriptional programs that guide phenotypic diversity have demonstrated the possibility of expanding the population of brown adipocytes in rodent models. Expanded populations of brown and beige adipocytes will require tight control of their metabolic activity, which might be achieved by selective neural activation, tissue-selective signaling or direct activation of lipolysis, which supplies the central fuel of thermogenesis.