Regulation of brown adipose tissue activity in humans by glucocorticoids

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Brown fat, also known as brown adipose tissue (BAT), is a unique tissue which functions to promote energy expenditure to raise body temperature. This type of fat has been extensively studied in small animals such as mice and is very important in these animals, as mice lacking BAT become obese. However brown fat has only recently been discovered in adult humans, and the importance of BAT and how it is controlled in humans is unclear. The current methods available to detect BAT activity in humans are inadequate, therefore this proposed project aims to build on existing tools and develop new techniques to determine the importance of BAT to energy expenditure in healthy humans. BAT biopsies will also be obtained from patients undergoing surgery and this tissue will be grown in culture dishes to investigate the important processes controlling its activation. Glucocorticoids are a type of steroid hormone which cause obesity if levels are persistently elevated. Glucocorticoids suppress energy production by brown fat in small animals, and we will use our new techniques to test whether glucocorticoids also suppress BAT activity in humans. The effect of glucocorticoids on the tissue biopsies will also be examined to discover the important pathways controlling energy expenditure in BAT. These studies will tell us whether blocking glucocorticoid action or other pathways in brown fat may increase energy expenditure in humans, and thereby treat obesity.