Background: Brown adipose tissue (BAT) is a novel player in energy metabolism by combusting glucose and lipids into heat, and central agonism of the glucagon-like peptide 1 receptor (GLP-1R) activates BAT in mice. In patients with type 2 diabetes, GLP-1R agonists lower blood glucose and lipid levels and reduce body weight. Therefore, we hypothesized that the GLP-1R agonist exenatide activates BAT in humans and thereby contributes to an improved nutrient metabolism.

Methods: Exenatide (Bydureon, 2 mg subcutaneous once weekly) was administered to 24 nondiabetic young men (age 27±3 years, BMI 24.3±2.6 kg/m²) for 12 weeks. Before and after treatment, BAT was visualized by ¹⁸F-fluorodeoxyglucose PET/CT scan and resting energy expenditure (indirect calorimetry), body composition (bio-impedance analysis) and fasting plasma glucose and serum lipids were determined.

Results: Exenatide decreased body weight (-1.5±2.0 kg, p<0.01), and improved serum triglycerides (0.7±0.3 vs 0.8±0.3 mmol/L, p<0.05), total cholesterol (4.2±0.7 vs 4.5±0.7 mmol/L, p<0.01) and LDL-cholesterol (2.7±0.6 vs 2.9±0.6 mmol/L, p<0.05). No significant change was observed in plasma glucose (4.6±0.3 vs 4.7±0.3 mmol/L, p=0.09) or resting energy expenditure (1779±262 vs 1822±233 kcal/day, p=0.14). Notably, exenatide increased BAT volume (117±73 vs 94±80 mL, p<0.05), which strongly positively correlated with ¹⁸F-fluorodeoxyglucose uptake in BAT (SUVmean: R²=0.67, p<0.0001).

Conclusion: We show for the first time that exenatide increases BAT activity in nondiabetic young men. We anticipate that GLP-1R-targeted therapy may improve cardiometabolic health in type 2 diabetes at least partly by activating BAT.

Trial number: NCT03002675