Roles for Prlhr/GPR10 and Npffr2/GPR74 in feeding responses to PrRP

Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS^Prlh cells). Not only does the artificial activation of NTS^Prlh cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS^Prlh neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We set out to determine roles for putative PrRP receptors in the response to NTS PrRP and exogenous PrRP-related peptides.

We used animals lacking PrRP receptors GPR10 and/or GPR74 (encoded by Prlhr and Npffr2, respectively) to determine roles for each in the restraint of food intake and body weight by the increased expression of Prlh in NTS^Prlh neurons (NTS^PrlhOX mice) and in response to the anorectic PrRP analog, p52.

Although Prlhr played a crucial role in the restraint of food intake and body weight in HFD-fed control animals, the combined absence of Prlhr and Npffr2 was required to abrogate the restraint of food intake in NTS^PrlhOX mice. p52 suppressed feeding independently of both receptors, however.

Hence, each receptor can participate in the NTS^Prlh-mediated suppression of food intake and body weight gain, while PrRP analog treatment can mediate its effects via distinct systems. While Prlhr plays a crucial role in the physiologic restraint of weight gain, the action of either receptor is capable of ameliorating obesity in response to enhanced NTS^Prlh signaling.