Endocrine Abstracts

The obesity epidemic has underlined the need for new treatments to aid weight loss and prevent the associated cardiometabolic sequelae of obesity. The relatively recent discovery of brown adipose tissue (BAT) in adult humans has revived interest in activating this tissue to increase energy expenditure as a novel treatment for these conditions. BAT is a thermogenic organ that generates heat to maintain body temperature in a cold environment. While BAT mass and activity are reduced in obesity, BAT is a plastic organ and activity can be increased in response to certain stimuli such as repeated cold exposure. In addition, the presence of BAT in obese subjects is associated with improved metabolic health and reduced incidence of cardiovascular disease. Therefore, it is important to determine how to safely increase BAT mass and thermogenesis to determine its therapeutic potential. However, our understanding of the pathways regulating human BAT remains limited, in part due to its location and the difficulty in quantifying activity in vivo. To improve our understanding of human brown adipose tissue function, we have performed a series of physiological studies in healthy volunteers using techniques such as PET imaging, microdialysis and thermal imaging. We have determined key differences in the regulation of brown adipose tissue function between species, such as identifying how glucocorticoids regulate brown adipose tissue activation in humans. We have also determined how brown adipose tissue utilises energy substrates to fuel thermogenesis. Most recently, we have undertaken hypothesis-free transcriptomics in human brown adipocytes to identify novel pathways regulating BAT function and have demonstrated their relevance in vivo. Understanding the pathways regulating cold-induced thermogenesis in humans may ultimately lead to novel therapies to enhance energy expenditure and improve metabolic function.