Thermogenesis activated by central melanocortin signaling is dependent on neurons in the rostral raphe pallidus (rRPa) area

The central melanocortin system plays a critical role in regulation of energy balance, including thermogenesis in brown adipose tissue (BAT). Activation of the hypothalamic melanocortin signaling stimulates sympathetically-mediated interscapular BAT (IBAT) thermogenesis. The rostral raphe pallidus (rRPa) and adjacent area have been proposed as the location of sympathetic premotor neurons for the central nervous system (CNS) control of IBAT thermogenesis. To determine if neuronal activity in rRPa area is required for the central melanocortin-induced thermogenesis, we studied the effects of inhibition of the activity of neurons in the rRPa area on the sympathetic nerve activity (SNA) to IBAT evoked by lateral ventricular injection of the melanocortin 3/4 receptor (MC3/4R) agonist, MTII, in urethane-chloralose-anesthetized rats and the effects on O2 consumption induced by third or fourth ventricular injection of MTII in conscious freely moving mice. Icv injection of MTII (1 nmol) significantly increased rat IBAT SNA (+ 741% of control). Both third and fourth ventricular injections of MTII (1 nmol) significantly increased O2 consumption in conscious C57BL/6J mice (45% higher than that of saline control for third ventricular injection and 44% higher than that of saline control for fourth ventricular injection). The increases in IBAT SNA and in O2 consumption were reversed by inhibition of neurons in the rRPa and adjacent area with microinjections of glycine or muscimol into rRPa. These results suggest that the neurons in the RPa and its immediate vicinity play an essential role in mediating the increase in IBAT thermogenesis induced by activation of central melanocortin signaling.