Figure 4.

Signaling through type 1 BMP receptors is required for the ability of central BMP7 to increase energy expenditure and drive sympathetic nerve activity in BAT. (A) In control C57BL/6 mice acutely treated with 2 μg in 2 μL of BMP7 by the i.c.v. route, there was a transient and significant increase in energy expenditure above basal levels, as measured by heat (left) in CLAMS metabolic cages. There was no difference in RER between groups (right) (N = 6 mice per group.) The vertical line indicates i.c.v. injection time, and all injections were between 8 am and 1 pm in the fed state. (B) When mice were pretreated i.c.v. with LDN, a potent and selective inhibitor of type 1 BMP receptor signaling, 1.5 hours before BMP7, the i.c.v. BMP7 delivery was no longer able to acutely increase Vo₂ (N = 3 mice per group). Interaction P value was not significant: P = 0.3025. The vertical line indicates i.c.v. injection time for injection 2. All injections were between 8 am and 1 pm in the fed state. LDN treatment alone could not be run because of space limitations in the metabolic cages. (C) Representative examples of 1-minute segments of BAT SNA in the baseline condition just before administration of BMP7 (10 mg in 10 μL; baseline panels to the left) and 30 minutes after BMP7 (panels to the right), in either naive rats (no pretreatment) or rats pretreated 1 hour before with LDN (10 μL, 100 mM, i.c.v.). (D) Mean ± standard error of the mean (SEM) of the BAT SNA 30 minutes after BMP7 administration (10 mg in 10 μL, i.c.v.), as a percentage of the baseline activity in rats receiving no pretreatment (N = 5) and in rats pretreated with LDN (10 μL, 100mM, i.c.v.) 1 hour before the BMP7 administration (N = 4). (E) Mean ± SEM of the change in interscapular BAT temperature (TBAT) evoked by i.c.v. administration of BMP7 in rats receiving no pretreatment or in rats pretreated with LDN (10 μL, 100 mM, i.c.v.) 1 hour before the BMP7 administration. *Indicates significance where P < 0.05. Error bars represent standard error of the mean. B7, BMP7; LDN, LDN193189; Pre-Tx, pretreatment; SNA, sympathetic nerve activity; Veh, vehicle.