Endocrine Abstracts (2015) 38 OC4.5 | DOI: 10.1530/endoabs.38.OC4.5

Glucagon increases energy expenditure independently of brown adipose tissue activation in humans

Chioma Izzi-Engbeaya1, Victoria Salem1, Rajveer Atkar1, Christopher Coello2, David Thomas3, Alexander Comninos1, Adam Buckley1, Eugenii Rabiner2, Roger Gunn2, Tricia Tan1, Stephen Bloom1 & Waljit Dhillo1

1Section of Investigative Medicine, Imperial College London, London, UK; 2Imanova Imaging Centre, London, UK; 3Department of Computing, Imperial College London, London, UK.

Background: Obesity is a global health concern. Elevating energy expenditure (EE) would be a highly effective treatment approach to treat obesity but no current drugs can safely achieve this. Cold exposure potently increases EE through brown adipose tissue (BAT) thermogenesis in humans. Glucagon elevates EE via BAT in rodents but the mechanism in humans is unknown. We investigated for the first time the mechanism by which glucagon increases EE in humans.

Methods: Eleven volunteers underwent measurement of EE using an indirect calorimeter at the start and end of three interventions: i) cold exposure; ii) control (vehicle) infusion at 23 °C; and iii) glucagon infusion at 23 °C. On each visit thermal images of the neck were taken – an increase in temperature is a non-invasive measure of increased BAT activity. All 11 volunteers also underwent a FDG PET–CT scan with cold exposure. In those in which this confirmed cold-induced BAT activity (n=8), they had a second PET–CT scan with either vehicle (n=4) or glucagon (n=4) infusion (23 °C).

Results: EE rose by 14% with cold exposure and 15% following glucagon infusion (P<0.05 vs control). BAT depots identified on the cold scan had significantly (4×) higher metabolic activity than on the vehicle or glucagon infusion scans, which were not significantly different from each other. There was a 0.31 °C rise (P<0.001) in neck temperature on thermal images after cold exposure in the BAT positive cohort but not after glucagon or vehicle infusion.

Conclusions: Glucagon and cold exposure have a similar effect in stimulating energy expenditure but glucagon has no effect on the metabolic activity of classical adult supraclavicular BAT compared with cold exposure. This information is of importance to the development of better targeted and safe treatments designed to combat obesity through upregulation of energy expenditure.