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SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level
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-...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553869/ http://dx.doi.org/10.1210/jendso/bvad114.1378 |
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author | Qin, Xiangfeng Ye, Cheng He, Mulan Wan Ko, Wendy Kit Wong, Anderson On-Lam |
author_facet | Qin, Xiangfeng Ye, Cheng He, Mulan Wan Ko, Wendy Kit Wong, Anderson On-Lam |
author_sort | Qin, Xiangfeng |
collection | PubMed |
description | 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 MEK(1/2), ERK(1/2) and P(38)(MAPK). 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 & P(38)(MAPK) pathways. Presentation: Saturday, June 17, 2023 |
format | Online Article Text |
id | pubmed-10553869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105538692023-10-06 SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level Qin, Xiangfeng Ye, Cheng He, Mulan Wan Ko, Wendy Kit Wong, Anderson On-Lam J Endocr Soc Non-steroid Hormone Signaling 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 MEK(1/2), ERK(1/2) and P(38)(MAPK). 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 & P(38)(MAPK) pathways. Presentation: Saturday, June 17, 2023 Oxford University Press 2023-10-05 /pmc/articles/PMC10553869/ http://dx.doi.org/10.1210/jendso/bvad114.1378 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Non-steroid Hormone Signaling Qin, Xiangfeng Ye, Cheng He, Mulan Wan Ko, Wendy Kit Wong, Anderson On-Lam SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title | SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title_full | SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title_fullStr | SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title_full_unstemmed | SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title_short | SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level |
title_sort | sat029 goldfish phoenixin: role in feeding control and its regulation at the hepatic level |
topic | Non-steroid Hormone Signaling |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553869/ http://dx.doi.org/10.1210/jendso/bvad114.1378 |
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