NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity.

Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; Calcr cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (Prlh) neurons represent a subset of Calcr cells and that Prlh expression in these cells restrains body weight gain in the face of high fat diet challenge in mice. To understand the relationship of Prlh cells to hypothalamic feeding circuits, we determined the ability of Prlh-mediated signals to overcome enforced activation of AgRP neurons.

Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice.

Leptin receptor-expressing (LepRb-expressing) neurons of the nucleus tractus solitarius (NTS; LepRbNTS neurons) receive gut signals that synergize with leptin action to suppress food intake. NTS neurons that express preproglucagon (Ppg) (and that produce the food intake-suppressing PPG cleavage product glucagon-like peptide-1 [GLP1]) represent a subpopulation of mouse LepRbNTS cells. Using Leprcre, Ppgcre, and Ppgfl mouse lines, along with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we examined roles for Ppg in GLP1NTS and LepRbNTS cells for the control of food intake and energy balance.

Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr neurons decreased food intake and body weight but (unlike neighboring Cck cells) failed to promote aversion, revealing that Calcr neurons mediate a non-aversive suppression of food intake.