Rxfp4, also known as Relaxin Family Peptide Receptor 4, is a G protein-coupled receptor in the relaxin family. It is the cognate receptor of insulin-like peptide 5 (INSL5), and the INSL5-Rxfp4 system may play a role in linking energy availability, homeostasis, and inflammation. It is involved in regulating immune response, potentially via decreasing pro-inflammatory cytokines production and may be related to the stress response through the HPA axis. It may also signal through sensory neurons on the vagus nerve to the CNS, and have local autocrine/paracrine roles in the intestinal tract and immune cells [1].

In Rxfp4-knockout mice, the high-fat diet (HFD) preference observed in wild-type mice is altered. Using a Rxfp4-Cre mouse model, researchers found that Rxfp4-expressing neurons in the ventromedial hypothalamus (RXFP4VMH) modulate food intake and preference. Chemogenetic inhibition of Rxfp4-expressing cells increased intake of HFD and highly palatable liquid meal (HPM), while activation reduced their intake and motivation to obtain HPM. This indicates that hypothalamic Rxfp4 signalling is a target for feeding behavior manipulation [2].

In conclusion, Rxfp4, through its interaction with INSL5, is involved in multiple physiological processes. The use of Rxfp4-knockout and Rxfp4-Cre mouse models has revealed its role in regulating food intake and preference, suggesting its potential as a target for treating disorders related to feeding behavior.

References:

1. Hechter, Drake, Vahkal, Brett, Tiede, Tiana, Good, Sara V. 2022. Reviewing the physiological roles of the novel hormone-receptor pair INSL5-RXFP4: a protective energy sensor? In Journal of molecular endocrinology, 69, R45-R62. doi:10.1530/JME-21-0241. https://pubmed.ncbi.nlm.nih.gov/35521762/

2. Lewis, Jo E, Woodward, Orla Rm, Nuzzaci, Danaé, Gribble, Fiona M, Reimann, Frank. 2022. Relaxin/insulin-like family peptide receptor 4 (Rxfp4) expressing hypothalamic neurons modulate food intake and preference in mice. In Molecular metabolism, 66, 101604. doi:10.1016/j.molmet.2022.101604. https://pubmed.ncbi.nlm.nih.gov/36184065/