CNS β 3 -adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight

Pharmacological β -adrenergic receptor (β AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β AR agonists is mediated solely through activation of β ARs in adipose tissue. However, β ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β ARs. Therefore, this study aimed to elucidate whether CNS β ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β AR activation.