The Thermogenic Effect of Mirabegron Ingestion During Cool Conditions

Purpose: Mirabegron (MIRA) activates beta-3-adrenergic receptors on brown adipose tissue (BAT). A single dose of MIRA increases energy expenditure (EE) and supraclavicular skin temperature (T sc , indicator of BAT activation) for up to 4 h in a thermoneutral environment. It is not known if the thermogenic effects of MIRA extend to a cool environment during extended exposures. We tested the hypothesis that EE and BAT activity during a 6 h cool environment exposure would be greater after a single dose of MIRA versus a placebo (PLA). Methods: 8 healthy adults (age: 22±2 y; BMI: 25±4 kg/m 2 , 4 women) completed two, double-blind, randomized study visits: ingestion of 100 mg of MIRA or PLA. 30 min after ingestion, subjects rested in a semi-recumbent position for 6 h in a whole-body indirect calorimeter (20°C, 50% RH). Total EE was calculated for each 6 h exposure (kcal). Rate of EE (kcal/min), O 2 consumption (VO 2 ; ml/kg/min), CO 2 production (VCO 2 ; ml/kg/min), and respiratory exchange ratio (RER) mean values were calculated for the last 10 min of each 30 min timepoint. BAT activity was assessed via infrared thermography of T sc every 30 min and expressed relative to sternal skin temperature, which served as a control. Mean skin (T sk ) temperature, calculated using 12 sites, and rectal temperature (T c ) were measured every 30 min. Thermal comfort (1=comfortable, 4=very uncomfortable) and sensation (1=cold, 7=hot) were measured every 30 min. Values are reported as mean±SD. Results: Total EE was greater in MIRA vs PLA (480±82 vs 452±69 kcal; condition effect p=0.003). Rate of EE (1.32±0.07 vs 1.24±0.03 kcal/min; p=0.005), VO 2 (3.7±0.5 vs 3.5±0.4 ml/kg/min; condition effect p=0.015), and VCO 2 (2.9±0.4 vs 2.8±0.4 ml/kg/min; condition effect p=0.002) were greater in MIRA vs PLA but did not differ between conditions for RER (MIRA: 0.79±0.01 vs PLA: 0.79±0.01; condition effect p=0.391). BAT activity did not differ between conditions (MIRA: 2.5±1.1 vs PLA: 2.3±1.1°C; condition effect p=0.318). T sk was greater in MIRA vs PLA (30.7±0.2 vs 30.4±0.1°C; condition effect p=0.037) but did not differ between conditions for T c (MIRA: 36.9±0.2 vs PLA: 36.8±0.4°C; condition effect p=0.303). Thermal comfort (MIRA: 1.9±0.5 vs PLA: 1.7±0.4; condition effect p=0.082) and sensation (MIRA: 2.6±0.9 vs PLA: 2.6±0.9; condition effect p=0.999) did not differ between conditions. Conclusions: Data indicates that 100 mg of MIRA elicits greater EE and attenuated the decrease inT sk during exposure to a cool environment vs PLA. However, BAT activity and perceptions did not differ between conditions.MIRA might be useful tothermal resiliency. Funded by: Office of Naval Research N00014-21-1-2276 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.