Physiological and metabolic functions of the β3-adrenergic receptor and an approach to therapeutic achievements.

A specific type of beta-adrenergic receptor was discovered in the decade of 1980s and subsequently recognized as a new type of beta-adrenergic receptor, called beta₃-adrenoceptor (β₃-AR). β₃-AR expresses in different tissues, including adipose tissue, gall bladder, stomach, small intestine, cardiac myocytes, urinary bladder, and brain. Structurally, β₃-AR is very similar to β₁- and β₂-AR and belongs to a G-protein coupled receptor that uses cAMP as an intracellular second messenger. Alternatively, it also activates the NO-cGMP cascade. Stimulation of the β₃-AR increases lipolysis, fatty acid oxidation, energy expenditure, and insulin action, leading to anti-obesity and anti-diabetic activity. Moreover, β₃-AR differentially regulates the myocardial contraction and relaxes the urinary bladder to balance the cardiac activity and delay the micturition reflex, respectively. In recent years, this receptor has served as an attractive target for the treatment of obesity, type 2 diabetes, congestive heart failure, and overactive bladder syndrome. Several β₃-AR agonists are in the emerging stage that can exert novel pharmacological benefits in different therapeutic areas. The present review focuses on the structure, signaling, physiological, and metabolic activities of β₃-AR. Additionally, therapeutic approaches of β₃-AR have also been considered.