Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis

Abstract

Significance Mirabegron as a β3-adrenoceptor agonist is a routinely prescribed drug for treating overactive bladder syndrome. However, the effect of this drug on off-targeted tissues and organs is largely unknown. In this study, we provide mechanistic insights on mirabegron-triggered atherosclerosis in causing potential cardiovascular and cerebrovascular diseases by activation of brown fat. Given that mirabegron can induce brown fat activation in adult human subjects, these findings are clinically relevant. Moreover, genetic mutations of low-density lipoprotein receptor (LDLR) frequently occur in human populations (1 in 300 humans carries LDLR mutations). If this population of patients receive mirabegron therapy, it would be of a high risk. This important issue has not been explored in clinical studies, and warrants further investigation.