Brown Fat: A Beta Way to Burn Calories, but Which Beta?

Abstract

Brown fat is a thermogenic tissue that may have therapeutic value for the treatment of obesity and diabetes. That brown fat is under sympathetic control is indisputable, but considerable controversy exists as to which of the beta-adrenergic receptor subtypes, b1AR, b2AR or b3AR, is the primary regulator. The purpose of the current study was to determine if co-administration of the b3AR agonist, mirabegron, would increase energy expenditure and brown fat activation more than non-selective bAR stimulation (isoproterenol) alone. 14 healthy, active young adults (8 males, 6 females) participated in a randomized crossover study. Energy expenditure in a temperature-controlled room (22.1 deg C, 48.5% relative humidity) was determined at rest and after ingestion of placebo or mirabegron (100mg), prior to intravenous administration of isoproterenol (30 minutes at 6, 12, and 24 ng/kg fat free mass/min). Brown fat activity was estimated using supraclavicular skin temperature assessed via infrared thermography. Baseline energy expenditure was not different ( P=0.42) prior to placebo (1487±106 kcal/day; (mean±SE)) and mirabegron (1424±104 kcal/day). Non-selective bAR stimulation increased energy expenditure above baseline (11.6±5.5, 15.2±6.3 and 20.1±6.0%; P<0.05); additional b3AR stimulation did not augment this response (18.0±3.8, 23.2±4.2 and 27.8±4.5%; P>0.05). Baseline supraclavicular skin temperature was not different ( P=0.95) prior to placebo (35.004±0.967◦C) and mirabegron (34.992±0.967◦C). Only the greatest dose of non-selective bAR stimulation increased supraclavicular skin temperature above baseline (0.236±0.082◦C); additional b3AR stimulation did not augment this response (0.100±0.082◦C; P=0.09). Co-administration of a b3AR agonist did not increase energy expenditure and brown fat activation more than non-selective bAR stimulation alone. These preliminary data imply that the b3AR might not be the primary regulator of brown fat activation in humans. Offce of Naval Research N00014-21-1-2276. This is the full abstract presented at the American Physiology Summit 2024 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.