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(NTs) cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (Prlh(NTs)) neurons represent a subset of Calcr(NTs) 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(NTs) cells to hypothalamic feeding circuits, we determined the ability of Prlh(NTs)-mediated signals to overcome enforced activation of AgRP neurons. We found that Prlh(NTs) neuron activation and Prlh overexpression in Prlh(NTs) cells abrogates AgRP neuron-driven hyperphagia and ameliorates the obesity of mice deficient in melanocortin signaling or leptin. Thus, enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity, demonstrating that NTS-mediated signals can override the effects of orexigenic hypothalamic signals on long-term energy balance.

Automated summary

The study shows that Prlh-expressing NTS neurons can suppress the effects of high-fat diets on body weight in mice, and activation of Prlh(NTs) neurons and overexpression of Prlh in these cells can abolish hyperphagia driven by AgRP neurons, improving obesity in mice deficient in melanocortin signaling or leptin. This suggests that enhancing Prlh-mediated neurotransmission from the NTS can attenuate hypothalamically-driven hyperphagia and obesity, overriding orexigenic signals in the long-term energy balance.