Activation of Brown Adipose Tissue Metabolism Using Mirabegron

In brief, participants will take part in 2 metabolic studies (A and B) performed in random order and at an interval of 7 to 14 days. Each metabolic study will last 8.5 hours with a baseline period of 2.5 hours. Participants will ingest either 200 mg of the ADRB3 agonist mirabegron (Myrbetriq, Astellas Pharma Canada) alone (study A) or in combination with 10 mg of bisoprolol, an ADRB1-antagonist (study B), at time 0.

The radioactive PET tracers (PET: positron emission tomography) used in this study are the [11C]-acetate and [18F]-FDG to estimate BAT oxidative metabolism and glucose metabolism, respectively. The perfusion of [6,6 D2]-glucose, [1,1,2,3,3-2H]-glycerol and [U-13C]-palmitate stable isotopes will also be performed in this study from time -150 min. to +300 min to examine the systemic appearance rate of glucose, glycerol and fatty acids, respectively. These studies will be almost identical (same perfusion of stable and radioactive tracers, same number of PET acquisitions) except for the drug which will be administered orally at time 0.

Inclusion criteria

• Healthy subjects with normal glucose tolerance determined according to an oral glucose tolerance test;
• BMI ≤ 30 kg/m2.

Exclusion criteria

• Plasma triglycerides > 5.0 mmol/L at fasting;
• More than 2 alcohol consumption per day;
• More than 1 cigarette per day;
• History of total cholesterol level > 7 mmol/L, of cardiovascular disease, hypertensive crisis;
• Treatment with fibrates, thiazolidinedione, insulin,betablockers or other drugs with effects on insulin resistance or lipid metabolism (exception for antihypertensive drugs, statins or metformin);
• Presence of a noncontrolled thyroid disease, renal or hepatic disease, history of pancreatitis, bleeding diatheses, cardiovascular disease or any other serious medical conditions;
• History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux having required a surgery, etc.); reflux having required a surgery, etc.);
• Presence of a pacemaker;
• Have undergone of PET study or CT scan in the past year;
• Chronic administration of any medication;