Feeding regulation by somatolactin in goldfish : insulin as a postprandial signal linking feeding and somatolactin expression at the hepatic level

Abstract

Somatolactin (SL), a member of the GH/PRL family, is produced in the posterior pituitary of fish species and is involved in a wide spectrum of biological functions. In goldfish, two isoforms of SL, SLα and SLβ, have been identified and their signals could also be located in the liver, although little/no information is available regarding the functions/regulation of extra-pituitary SL in fish models. In the present study, feeding in goldfish was shown to up-regulate SLα and SLβ gene expression in the liver as well as in the pituitary with transient rises of their protein levels in the plasma. Using recombinant proteins of goldfish SLα and SLβ produced in E. coli, IP and ICV injection of SLs were effective in reducing food intake and feeding behavior in goldfish. ICV injection of SLα and SLβ could also inhibit gene expression of AgRP, apelin, NPY and orexin with parallel stimulation in, CART, CCK, CRH and POMC expression in the brain areas involved in feeding control and similar responses could be observed in the primary culture of goldfish brain cells with SLα and SLβ treatment. In goldfish, insulin has been recently confirmed to act as a functional link between food intake and regulation of feeding regulators. By IP injection of insulin, SLα and SLβ transcriptional levels were found to be elevated in the liver as well as in the pituitary similar to the effects caused by feeding. Although insulin treatment did not alter SL gene expression/secretion in goldfish pituitary cell culture, similar treatment in a primary culture of goldfish hepatocytes could stimulate SLα and SLβ release with parallel rises of their respective transcript expression. Using a pharmacological approach, insulin-induced SLα and SLβ mRNA expression at the hepatic level were shown to be mediated by insulin receptor (to a lesser extent by IGF-I receptor) functionally coupled with MEK1/2/ERK1/2, p38 MAPK and PI3K/Akt cascades. The present findings, as a whole, suggest that insulin signal caused by food intake may trigger SLα and SLβ expression and secretion in the liver, which may contribute to the satiation response induced by feeding via differential regulation of orexigenic and anorexigenic signals within the CNS of goldfish.