Novel function of spexin as a satiety factor in feeding control

Abstract

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel neuropeptide discovered recently using the bioinformatic approach. Except for mammals, SPX has not been reported in lower vertebrates including fish and amphibians. Following its discovery, the biological functions of this peptide in both higher and lower vertebrates are still largely unknown.

To examine the structure and functions of SPX in fish model, molecular cloning of goldfish SPX has been performed and found to be highly comparable to its mammalian counterparts. In goldfish, broad expression of SPX transcripts has been found in various tissues. In vivo feeding studies have revealed that SPX mRNA levels in the telencephalon, optic tectum and hypothalamus of goldfish brain could be elevated by food intake. Brain injection of goldfish SPX, however, inhibited both basal and NPY- and orexin-induced feeding behaviour and food consumption. Similar treatment has also reduced transcript expression of NPY, AGRP and apelin with concurrent rises in CCK, CART, POMC, MCH and CRH mRNA levels in different brain areas examined. The differential effects of goldfish SPX on NPY, CCK and MCH transcript expression could also be noted in vitro in goldfish brain cell culture.

In mice, SPX has been also found to be expressed within the brain-gut axis, including the stomach and specific neuronal subpopulations within the hypothalamus, including the ARC, PVN, DMN, and VMN. Similar to goldfish, feeding has shown to affect SPX mRNA and protein expression. Fasted animals have lower SPX mRNA in the stomach, and lower SPX protein levels in the serum and glandular stomach; the opposite effects have been noted in ad libitumfed animals. Both IP and ICV injection of SPX could produce a short-term feeding inhibitory effect. Furthermore, ICV administration of SPX could also downregulate hypothalamic expression of NPY, NPY5R, AGRP, and GHSR mRNA, and upregulate leptin receptor and MC4R gene expression concurrently.

Taken together, these findings suggests that SPX may act as a satiety factor in vertebrate species. Apparently, SPX expression could be induced by feeding and the neuropeptide could act centrally to inhibit feeding by differentially regulating orexigenic and anorexigenic signals within the CNS.