The metabolic effects of mirabegron are mediated primarily by β₃‐adrenoceptors

Abstract

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β3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis

“…Our data emphasize that mirabegron ( 82 ), a drug in current clinical use, increases lipolysis and thermogenesis in human brown/beige adipocytes specifically through activation of the β 3 -AR. These data are in accordance with our clinical studies where we observed that acute mirabegron treatment increases FFA and energy expenditure ( 38 , 39 ).…”

Effect of β1/β2‐adrenoceptor blockade on β3‐adrenoceptor activity in the rat cremaster muscle artery

“…Isoprenaline has a reported pKi of 5.3–3.4 for the rat β 3 ‐adrenoceptor (Alexander, Christopoulos, et al, 2019a; Popp et al, 2004), concentrations well beyond that required for full dilation of the cremaster muscle artery, perhaps suggesting why isoprenaline did not appear to activate β 3 ‐adrenoceptor in the current study. β 3 ‐adrenoceptor‐mediated isoprenaline responses at lower concentrations (pEC 50 7–8) have been observed in a variety of cell and tissue types (Arch & Kaumann, 1993; Dehvari et al, 2020; Hutchinson et al, 2001), although reported pEC 50 values for arterial relaxation are around 5 (Brawley et al, 2000; Flacco et al, 2013; Riedel et al, 2019). Relative receptor expression levels may also contribute to the lack of β 3 ‐adrenoceptor‐mediated isoprenaline effects in the present study.…”

“…Michel & Korstanje, 2016). Other possible clinical applications of β 3 -adrenoceptor ligands are emerging (Arioglu-Inan et al, 2019;Dehvari et al, 2018Dehvari et al, , 2020, particularly in relation to the cardiovascular system. Current clinical trials are investigating the efficacy of mirabegron as an inotropic agent in heart failure (BEAT-HF; Bundgaard et al, 2017), in preventing hypertension-induced ventricular hypertrophy and diastolic dysfunction (Beta3-LVH;Pouleur et al, 2018) and in relieving heart failure-related pulmonary hypertension (SPHERE-HF; Garcia-Lunar et al, 2020).…”

Myosin 1c: A novel regulator of glucose uptake in brown adipocytes

“…Importantly, we did not observe this effect in white adipocytes. Although the adrenergic pathway is fully functional in white adipocytes leading to cAMP production, PKA activation, and lipolysis [ 41 ], it fails to induce glucose uptake in white adipocytes and WAT [ 34 , 60 ]. However, in contrast to GLUT4, the basal expression levels of GLUT1 in white adipocytes are known to be higher than in brown [ 22 ], in agreement with our data.…”