β3-adrenergic agonists and "browning" of the white adipose tissue: Influence on energy balance and obesity associated metabolic risks
Abstract
Currently available antiobesity drugs affect mainly energy intake and not energy expenditure. Trials with β3-adrenergic receptor agonists increasing energy expenditure by activation of brown adipose tissue have been conducted over30 years.
However, most of these drugs were not selective for β3 receptors and failed in human trials due to untoward cardiovascular side-effects. Both experimental and human studies recently demonstrated that not only brown adipocytes but also beige adipocytes may possess thermogenic, antidiabetic and muscle protective effects. "Browning" of adipose tissue with occurrence of beige adipocytes in white adipose tissue may be induced by cold, hormones, several dietary factors and β3-agonists.
Two selective β3-adrenoreceptor agonists, mirabegron and vibegron, have been used for the treatment of overactive bladder without significant increases in pulse rate and blood pressure if the recommended prescribed dose of drug was applied. Activation of human brown adipocytes with an increase in resting metabolic rate and supraclavicular skin temperature was observed after a single dose of mirabegron.
Moreover, recent studies in obese, insulin resistant subjects demonstrated that chronic administration of mirabegron in a dose used for the treatment of overactivec bladder (50 mg/day) was associated with induction of beige adipocytes in human subcutaneous white adipose tissue. Potential use of novel β3-agonists to oppose energy efficiency in response to weight loss therapy and to improve metabolic profile in obesity is discussed in the review.