52. The Novel Adrenergic Agonist ATR-127 Targets Skeletal Muscle and Brown Adipose Tissue to Tackle Diabesity and Steatohepatitis

Talamonti E., Davegardh J., Kalinovich A., van Beek S. M. M., Dehvari N., Halleskog C., Bokhari H. M., Hutchinson D. S., Ham S., Humphrys L. J., Dijon N. C., Motso A., Sandstrom A., Zacharewicz E., Mutule I., Suna E., Spura J., Ditrychova K., Stoddart L. A., Holliday N. D., Bengtsson T. Molecular Metabolism, 2024, 101931.
DOI: 10.1016/j.molmet.2024.101931.

 

Abstract

Simultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs – and thus inducing cardiovascular complications – are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models.