A hypothalamic neuropeptide, RF-amide related peptide-3 (RFRP-3), the mammalian ortholog of the avian gonadotropin-inhibitory hormone (GnIH) has inhibitory signals for reproductive axis via G-protein coupled receptor 147 in mammals. Moreover, RFRP-3 has orexigenic action but the mechanism involved in energy homeostasis and glucose metabolism is not yet known. Though, the RFRP-3 modulates orexigenic action in co-operation with other neuropeptides, which regulates metabolic cues in the hypothalamus. Administration of GnIH/RFRP-3 suppresses plasma luteinizing hormone, at the same time stimulates feeding behavior in birds and mammals. Likewise, in the metabolically deficient conditions, its expression is up-regulated suggests that RFRP-3 contributes to the integration of energy balance and reproduction. However, in many other metabolic conditions like induced diabetes and high-fat diet obesity, etc. its role is still not clear while, RFRP-3 induces the glucose homeostasis by adipocytes is reported. The physiological role of RFRP-3 in metabolic homeostasis and the metabolic effects of RFRP-3 signaling in pharmacological studies need a detailed discussion. Further studies are required to find out whether RFRP-3 is associated with restricted neuroendocrine function observed in type II diabetes mellitus, aging, or sub-fertility. In this context, the current review is focused on the role of RFRP-3 in the above-mentioned mechanisms. Studies from search engines including PubMed, Google Scholar, and science.gov are included after following set inclusion/exclusion criteria. As a developing field few mechanisms are still inconclusive, however, based on the available information RFRP-3 seems to be a putative tool in future treatment strategies towards metabolic disease.
Keywords: Energy homeostasis; GPR147; Metabolic deficient condition; RFRP-3/GnIH.