Brown Adipose Tissue In Humans: A New Target for Anti-Obesity Therapy

Abstract

This chapter describes work to combat obesity and obesity-related diseases by increasing energy expenditure. We build on a recent finding by others and us that has demonstrated the existence of significant amounts of metabolically active brown adipose tissue (BAT) in healthy adult humans. 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. The identification of BAT in adult humans opens completely new avenues of therapeutic intervention, which will be discussed in the context of previous findings regarding forkhead genes and their importance for recruitment of BAT in vivo. FOXC2 acts both as a “sensitizer” of PKA signaling in BAT and a regulator of BAT vascularization. In light of this, human BAT function is a highly relevant medical issue, and points of interest are: 1) to further understand substrate metabolism and the systemic importance of human BAT; 2) to investigate the possibility of distinct classes of human BAT cells; 3) to characterize the gene regulatory networks that control BAT differentiation and metabolic activity, and 4) to identify putative drug targets for BAT activation and to explore their physiological importance.