Endocrine Abstracts

Brown adipose tissue (BAT) may directly dissipate energy into heat and is associlated with a metabolically favorable phenotype. Cold exposure activates BAT via the sympathetic nervous system and its transmitter norepinephrine. In rodents, the activation is facilitated by the β3-adrenoreceptor (β3-AR). In humans treatment with the β3-AR agonist mirabegon leads to a rather weak activation of BAT as compared to a cold stimulus. In vitro studies in cell lines from human BAT and have pointed towards the β2-AR as a possible activator. We studied the effect of an infusion with the potent and selective β2-AR agonist fenoterol on human resting energy expenditure (REE) and BAT activity compared to a mild cold stimulus in normal weight volunteers. REE was measured continously with indirect calorimetry, skin and core temperature were recorded, and BAT activity was quantified in the supraclavicular BAT depot by 18F-FDG-PET/CT after each intervention. Blood was sampled for metabolic analysis. Resting EE at baseline was similar before the two interventions. Cold exposure resulted in a mean increase in EE of 195 kcal/24 h (P=0.044 vs baseline) and fenoterol infusion increased EE by 358 kcal/24 h (P<0.0001). The mean standardized uptake value (SUVmean) of supraclavicular BAT was 3,06 (IQR 2,19;3,64) g/ml after cold exposure but only 1,66 g/ml [1,63;1,70] after fenoterol infusion. Correspondingly, the active BAT volume was 90 (26;190) ml vs 3 (1;16) ml, respectively. Analysis of the lipidome revealed higher levels of mono- and poly-unsaturated fatty acids after both interventions, which was stronger after fenoterol than after cold exposure (P<0.0001). In contrast, in all other lipid categories, fenoterol failed to replicate the pattern, which a cold stimulus induces in the lipidome. The main side effect of fenoterol was a feeling of warmth and a mild tachycardia. In conclusion fenoterol increased REE more than cold exposure but did not activate human BAT. This indicates that the human β2-AR does not play an important role in BAT activation which is underscored by differential lipid profiles after both interventions. However, β2-AR mediated increases in REE might be an attractive therapeutic target to treat obesity.