SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level

Abstract Disclosure: X. Qin: None. C. Ye: None. M. He: None. W.K. Ko: None. A.O. Wong: None. Phoenixin (PNX), a novel peptide first identified by bioinformatics, is known to have pleiotropic functions and its biological actions are mediated via the orphan receptor GPR173. At present, the study of PNX in non-mammalian species, especially in lower vertebrates, is limited and hormone regulation of PNX as well as the post-receptor signalling involved are still unclear. Using goldfish as a model for bony fish, two forms of PNX, PNXa & b, and one form of GPR173 were cloned. Phylogenetic analysis confirmed that goldfish PNXa, PNXb & GPR173 could be clustered in respective clades of target genes in fish species. Alignment of a.a. sequences and 3D protein modelling also revealed that goldfish PNXa & b were highly comparable to PNX reported in other vertebrates. Using RT-PCR, PNXa/b & GPR173 were found to be ubiquitously expressed at tissue level. For functional testing, PNXa & b were synthesized and tested for their effects on feeding control by IP injection in goldfish. In this case, parallel rises in foraging behaviours and food intake were noted after PNX treatment. Similar results were also obtained with ICV injection of PNXa & PNXb, respectively. In goldfish, food intake could elevate plasma levels of glucose, insulin, growth hormone (GH) and IGF-I with parallel rises in transcript expression of GH in the pituitary and PNXa, PNXb, insulin & IGF-I mRNA in the liver. In goldfish hepatocytes, insulin and IGF-I were both effective in up-regulating PNXa & b mRNA expression via activation of IGF-I receptor (IGF1R) but not insulin receptor. Using a pharmacological approach, IGF-I induced PNXa & b gene expression could be blocked by the inhibitors for PI3K, Akt and mTor but not by the inhibitors for MEK1/2, ERK1/2 and P38MAPK. Our results, as a whole, indicate that (i) PNX & GPR173 are co-expressed in goldfish at tissue level & involved in feeding induction, presumably via central action in the brain, (ii) food intake can up-regulate hepatic expression of PNXa & b via insulin signal caused by glucose uptake and parallel activation of the GH/IGF-I axis after feeding, and (iii) hepatic expression of PNXa & b induced by insulin/IGF-I signal is mediated via IGF1R functionally coupled with the PI3K/Akt/ mTOR but not MEK/ERK & P38MAPK pathways. Presentation: Saturday, June 17, 2023