Abstract
Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; CalcrNTS cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (PrlhNTS) neurons represent a subset of CalcrNTS 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 PrlhNTS cells to hypothalamic feeding circuits, we determined the ability of PrlhNTS-mediated signals to overcome enforced activation of AgRP neurons. We found that PrlhNTS neuron activation and Prlh overexpression in PrlhNTS 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.
Highlights
Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; CalcrNTS cells) contribute to the long-term control of food intake and body weight
We previously demonstrated that CalcrNTS neurons mediate the non-aversive suppression of food intake and contribute to the longterm control of food intake and body weight[4]
To determine the potential role for prolactin releasing hormone (Prlh)-expressing NTS (PrlhNTS) neurons in this effect, we examined the ability of CNO-dependent PrlhNTS neuron activation in PrlhNTS-Dq mice to suppress fasting-induced mediobasal arcuate nucleus (ARC) FOS-IR (Supplementary Fig. 6A–G)
Summary
Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; CalcrNTS cells) contribute to the long-term control of food intake and body weight. To understand the relationship of PrlhNTS cells to hypothalamic feeding circuits, we determined the ability of PrlhNTS-mediated signals to overcome enforced activation of AgRP neurons. We found that PrlhNTS neuron activation and Prlh overexpression in PrlhNTS cells abrogates AgRP neuron-driven hyperphagia and ameliorates the obesity of mice deficient in melanocortin signaling or leptin. While brainstem circuits were previously thought to control only short-term parameters of food intake (rather than long-term feeding and energy balance), silencing CalcrNTS cells increases food intake and weight gain, especially in high fat diet (HFD)-fed animals[4]. Prlh, which is primarily expressed in the NTS, the lateral reticular nucleus (LRt) and the dorsomedial hypothalamic nucleus (DMH), modulates food intake and energy expenditure[9,10,11,12]
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