Leptin receptor signaling in the lateral parabrachial nucleus contributes to the control of food intake

Abstract

Pontine parabrachial nucleus (PBN) neurons integrate visceral, oral, and other sensory information, playing an integral role in the neural control of feeding. Current experiments probed whether lateral PBN (lPBN) leptin receptor (LepRb) signaling contributes to this function. Intra-lPBN leptin microinjection significantly reduced cumulative chow intake, average meal size, and body weight in rats, independent of effects on locomotor activity or gastric emptying. In contrast to the effects observed following LepRb activation in other nuclei, lPBN LepRb stimulation did not affect progressive ratio responding for sucrose reward or conditioned place preference for a palatable food. Collectively, results suggest that lPBN LepRb activation reduces food intake by modulating the neural processing of meal size/satiation signaling, and highlight the lPBN as a novel site of action for leptin-mediated food intake control.

Keywords: PBN; food intake; leptin; meal size; obesity.

Fig. 1.

Representative image of lateral pontine parabrachial nucleus (lPBN) injection site (black arrow) (A), and a schematic diagram of approximate injection sites in a cohort of rats in this study (B), numbers represent position (mm) relative to bregma, ● represents hits and X represents misses.

Fig. 2.

Leptin administration to the cerebral aqueduct did not affect cumulative chow intake.

Fig. 3.

lPBN leptin receptor (LepRb) activation reduced cumulative chow intake (A), 24-h change in body weight (B), and 24-h water intake (C) (means ± SE; *P < 0.05, **P < 0.01, ***P < 0.001).

Fig. 4.

lPBN LepRb activation reduced average meal size (A) but had no effect on average meal number (B) in animals maintained on chow (means ± SE; *P < 0.05, **P < 0.01).

Fig. 5.

lPBN LepRb activation reduced cumulative high-fat diet intake (A and B), with no effect on 24-h change in body weight (C) or 24-h water intake (D) (means ± SE; *P < 0.05).

Fig. 6.

lPBN leptin did not significantly affect average meal size (A and B) or average meal number (C and D) in animals maintained on high-fat diet, although there are trends for reductions in meal size at several time points.

Fig. 7.

lPBN LepRb activation did not affect total number of lever presses (A) or number or reinforcers earned (B) in a progressive ratio operant responding test. lPBN LepRb activation also did not affect shift in preference for a food-paired environment (C) or total distance traveled (D) in a conditioned place preference test.

Fig. 8.

lPBN LepRb activation did not affect gastric emptying.