Brown adipose tissue as a novel therapeutic target for obesity and type 2 diabetes

Brown adipose tissue as a novel therapeutic target for obesity and type 2 diabetes

Brown adipose tissue functions to increase energy expenditure to generate heat. Researchers at the University of Edinburgh are investigating how best to activate this tissue in humans as a novel therapy for obesity and type 2 diabetes.

The prevalence of obesity has increased dramatically over the last 30 years and most pharmacological agents developed to treat obesity have focused on limiting food intake. However, brown adipose tissue (BAT) is a special type of fat tissue very different to the normal fat we have in our body. The role of BAT is to increase energy expenditure to keep our bodies warm when we are in a cold environment. People who are of normal weight have more BAT than those with obesity, however most obese individuals have the ability to grow more BAT. Therefore, activating BAT is an exciting novel strategy to increase energy expenditure as a treatment for obesity and obesity-associated type 2 diabetes.  We currently have only limited knowledge of human BAT, so in our research we use bespoke human experimental techniques such as PET/CT, PET/MR, thermal imaging, primary human cell culture and respirometry in order to investigate how human BAT activation is controlled. We have identified key species-specific differences in the regulation of human BAT activation by glucocorticoids, highlighting the importance of studying this tissue in humans. In addition, we have developed entirely novel techniques to dissect human BAT physiology and cold-induced thermogenesis. We are currently investigating the key pathways responsible for activating BAT, with a view to developing new pharmacological agents to increase energy expenditure to treat human metabolic disease.

Key references:

Weir G, Ramage LE, Akyol M, Rhodes JK, Kyle CJ, Fletcher AM, Craven TH, Wakelin SJ, Drake AJ, Gregoriades ML, Ashton C, Weir N, van Beek EJR, Karpe F, Walker BR, Stimson RH. Substantial metabolic activity of human brown adipose tissue during warm conditions and cold-induced lipolysis of local triglycerides. Cell Metabolism 2018; 27(6): 1348-55.

Ramage LE, Akyol M, Fletcher AM, Forsythe J, Nixon M, Carter RN, van Beek EJR, Morton NM, Walker BR, Stimson RH. Glucocorticoids acutely increase brown adipose tissue activity in humans, revealing species-specific differences in UCP-1 regulation. Cell Metabolism 2016; 24(1): 130-41.

Principal Investigator, Co-Investigators, Other researchers

PI – Dr Roland Stimson

Associated researcher – Professor Nicholas Morton