Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure and heart rate, but not food intake

Bombesin-like receptor 3 (BRS3) is an orphan G protein-coupled receptor that regulates energy homeostasis and heart rate. We report that acute activation of Brs3-expressing neurons in the dorsomedial hypothalamus (DMH(Brs3)) increased body temperature (Tb), brown adipose tissue temperature, energy expenditure, heart rate and blood pressure, with no effect on food intake or physical activity. Conversely, activation of Brs3 neurons in the paraventricular nucleus of the hypothalamus (PVH(Brs3)) had no effect on Tb or energy expenditure, but suppressed food intake. Inhibition of DMH(Brs3) neurons decreased Tb and energy expenditure, suggesting a necessary role in Tb regulation. We found that the preoptic area provides major input (excitatory and inhibitory) to DMH(Brs3) neurons. Optogenetic stimulation of DMH(Brs3) projections to the raphe pallidus (RPa) increased Tb. Thus, DMH(Brs3)→RPa neurons regulate Tb, energy expenditure and heart rate, and PVH(Brs3) neurons regulate food intake. Brs3 expression is a useful marker for delineating energy metabolism regulatory circuitry.