Mirabegron and Brown Adipose Tissue

Obesity and type 2 diabetes (T2D) are emerging problems worldwide. In particular South Asian individuals (representing 20% of the world population) have an increased risk of obesity and related disorders. They are at higher risk for the development of T2D as compared to white Caucasians and develop T2D at a younger age and with lower BMI. The underlying mechanisms that might explain these ethnical differences have not been clarified or understood yet. As a consequence, treatment options are limited and unfocussed, and novel specific strategies are needed. Brown adipose tissue (BAT) has recently been discovered as a major player in energy metabolism in humans. In a process known as thermogenesis, BAT takes up fatty acids (FA) and glucose from the circulation and subsequently combusts FA and glucose into heat, thereby increasing energy expenditure and improving glucose and FA metabolism. Using 18F-fluorodeoxyglucose (18F-FDG) (positron emission tomography/computed tomography) PET-CT scan analysis investigators have recently shown that South Asian individuals have less brown adipose tissue (BAT) than white Caucasians. This might suggest that they have a lower energy metabolism, which could underlie their increased predisposition for obesity and the development of T2D. Activation of BAT, for example by cold exposure, was shown to have beneficial metabolic effects in humans. Cold acclimatization can increase BAT volume, nonshivering thermogenesis, glucose uptake by BAT, as well as decrease fat mass in healthy young men. Therefore activation of BAT is considered as a novel therapeutic target in the treatment of obesity and T2D. As cold exposure is not the most desired therapeutic strategy for humans, current pre-clinical research focuses on pharmacological activation of BAT. β3-receptor agonists can be used to mimic sympathetic innervation of BAT. Our recent studies using mice with a human-like lipoprotein profile showed that treatment with a β3-receptor agonist decrea