The chondrichthyan glucagon-like peptide 3 regulates hepatic ketone metabolism in the Pacific spiny dogfish Squalus suckleyi

Alyssa M Weinrauch; Ian A Bouyoucos; J Michael Conlon; W Gary Anderson

doi:10.1016/j.ygcen.2024.114470

The chondrichthyan glucagon-like peptide 3 regulates hepatic ketone metabolism in the Pacific spiny dogfish Squalus suckleyi

Alyssa M Weinrauch
, Ian A Bouyoucos
, J Michael Conlon
, W Gary Anderson

University of Manitoba

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

74 Downloads (Pure)

Abstract

Chondrichthyans have a novel proglucagon-derived peptide, glucagon-like peptide (GLP)-3, in addition to GLP-1 and GLP-2 that occur in other vertebrates. Given that the GLPs are important regulators of metabolic homeostasis across vertebrates, we sought to investigate whether GLP-3 displays functional actions on metabolism within a representative chondrichthyan, the Pacific spiny dogfish Squalus suckleyi. There were no observed effects of GLP-3 perfusion (10 nM for 15 min) on the rate of glucose or oleic acid acquisition at the level of the spiral valve nor were there any measured effects on intermediary metabolism within this tissue. Despite no effects on apparent glucose transport or glycolysis in the liver, a significant alteration to ketone metabolism occurred. Firstly, ketone flux through the perfused liver switched from a net endogenous production to consumption following hormone application. Accompanying this change, significant increases in mRNA transcript abundance of putative ketone transporters and in the activity of β-hydroxybutyrate dehydrogenase (a key enzyme regulating ketone flux in the liver) were observed. Overall, while these results show effects on hepatic metabolism, the physiological actions of GLP are distinct between this chondrichthyan and those of GLP-1 on teleost fishes. Whether this is the result of the particular metabolic dependency on ketone bodies in chondrichthyans or a differential function of a novel GLP remains to be fully elucidated. [Abstract copyright: Copyright © 2024 Elsevier Inc. All rights reserved.]

Original language	English
Article number	114470
Pages (from-to)	1-11
Number of pages	11
Journal	General and Comparative Endocrinology
Volume	350
Early online date	10 Feb 2024
DOIs	https://doi.org/10.1016/j.ygcen.2024.114470
Publication status	Published (in print/issue) - 1 May 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Inc.

Data Access Statement

I have shared the link to the data within the results section.

Funding

Funding was provided by the University of Manitoba Faculty of Science Fieldwork support program and a Natural Science and Engineering Research Council of Canada (NSERC) Discovery grant (#05348–15) to WGA and NSERC-PDF to AMW. Additional funding came from a Company of Biologists Travelling Fellowship (JEBTF2202664) awarded to AMW. We thank Jenna Drummond, Ameera Kingra, Jessica MacPherson, Ryan Wahl, and Dr. Alexandra Schoen for animal collection and maintenance. Thanks also to the staff of BMSC, with particular thanks to the animal care committee, Skipper Dave Porter, and Tao Eastham. Many thanks also to Drs. Ben Speers-Roesch and Jay Treberg for insights with CPT assay troubleshooting. The authors gratefully acknowledge that the Bamfield Marine Sciences Centre sits within the traditional territory of the Huu-ay-aht First Nations and the University of Manitoba campuses are located on the original lands of the Anishinaabeg, Cree, Oji-Cree, Dakota, and Dene peoples, and on the homeland of the Métis Nation. Funding was provided by the University of Manitoba Faculty of Science Fieldwork support program and a Natural Science and Engineering Research Council of Canada (NSERC) Discovery grant (#05348-15) to WGA and NSERC-PDF to AMW. Additional funding came from a Company of Biologists Travelling Fellowship (JEBTF2202664) awarded to AMW.

Funders	Funder number
JEBTF2202664
University of Manitoba
05348–15

Keywords

Intermediary metabolism
Liver
Elasmobranch
Ketones
Glucagon-like peptide
Spiral Valve

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ygcen.2024.114470

Dogfish GLP-3 MSAuthor Accepted Manuscript -, 1.55 MB

Cite this

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title = "The chondrichthyan glucagon-like peptide 3 regulates hepatic ketone metabolism in the Pacific spiny dogfish Squalus suckleyi",

abstract = "Chondrichthyans have a novel proglucagon-derived peptide, glucagon-like peptide (GLP)-3, in addition to GLP-1 and GLP-2 that occur in other vertebrates. Given that the GLPs are important regulators of metabolic homeostasis across vertebrates, we sought to investigate whether GLP-3 displays functional actions on metabolism within a representative chondrichthyan, the Pacific spiny dogfish Squalus suckleyi. There were no observed effects of GLP-3 perfusion (10 nM for 15 min) on the rate of glucose or oleic acid acquisition at the level of the spiral valve nor were there any measured effects on intermediary metabolism within this tissue. Despite no effects on apparent glucose transport or glycolysis in the liver, a significant alteration to ketone metabolism occurred. Firstly, ketone flux through the perfused liver switched from a net endogenous production to consumption following hormone application. Accompanying this change, significant increases in mRNA transcript abundance of putative ketone transporters and in the activity of β-hydroxybutyrate dehydrogenase (a key enzyme regulating ketone flux in the liver) were observed. Overall, while these results show effects on hepatic metabolism, the physiological actions of GLP are distinct between this chondrichthyan and those of GLP-1 on teleost fishes. Whether this is the result of the particular metabolic dependency on ketone bodies in chondrichthyans or a differential function of a novel GLP remains to be fully elucidated. [Abstract copyright: Copyright {\textcopyright} 2024 Elsevier Inc. All rights reserved.]",

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author = "Weinrauch, \{Alyssa M\} and Bouyoucos, \{Ian A\} and Conlon, \{J Michael\} and Anderson, \{W Gary\}",

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doi = "10.1016/j.ygcen.2024.114470",

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AU - Conlon, J Michael

AU - Anderson, W Gary

PY - 2024/5/1

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N2 - Chondrichthyans have a novel proglucagon-derived peptide, glucagon-like peptide (GLP)-3, in addition to GLP-1 and GLP-2 that occur in other vertebrates. Given that the GLPs are important regulators of metabolic homeostasis across vertebrates, we sought to investigate whether GLP-3 displays functional actions on metabolism within a representative chondrichthyan, the Pacific spiny dogfish Squalus suckleyi. There were no observed effects of GLP-3 perfusion (10 nM for 15 min) on the rate of glucose or oleic acid acquisition at the level of the spiral valve nor were there any measured effects on intermediary metabolism within this tissue. Despite no effects on apparent glucose transport or glycolysis in the liver, a significant alteration to ketone metabolism occurred. Firstly, ketone flux through the perfused liver switched from a net endogenous production to consumption following hormone application. Accompanying this change, significant increases in mRNA transcript abundance of putative ketone transporters and in the activity of β-hydroxybutyrate dehydrogenase (a key enzyme regulating ketone flux in the liver) were observed. Overall, while these results show effects on hepatic metabolism, the physiological actions of GLP are distinct between this chondrichthyan and those of GLP-1 on teleost fishes. Whether this is the result of the particular metabolic dependency on ketone bodies in chondrichthyans or a differential function of a novel GLP remains to be fully elucidated. [Abstract copyright: Copyright © 2024 Elsevier Inc. All rights reserved.]

AB - Chondrichthyans have a novel proglucagon-derived peptide, glucagon-like peptide (GLP)-3, in addition to GLP-1 and GLP-2 that occur in other vertebrates. Given that the GLPs are important regulators of metabolic homeostasis across vertebrates, we sought to investigate whether GLP-3 displays functional actions on metabolism within a representative chondrichthyan, the Pacific spiny dogfish Squalus suckleyi. There were no observed effects of GLP-3 perfusion (10 nM for 15 min) on the rate of glucose or oleic acid acquisition at the level of the spiral valve nor were there any measured effects on intermediary metabolism within this tissue. Despite no effects on apparent glucose transport or glycolysis in the liver, a significant alteration to ketone metabolism occurred. Firstly, ketone flux through the perfused liver switched from a net endogenous production to consumption following hormone application. Accompanying this change, significant increases in mRNA transcript abundance of putative ketone transporters and in the activity of β-hydroxybutyrate dehydrogenase (a key enzyme regulating ketone flux in the liver) were observed. Overall, while these results show effects on hepatic metabolism, the physiological actions of GLP are distinct between this chondrichthyan and those of GLP-1 on teleost fishes. Whether this is the result of the particular metabolic dependency on ketone bodies in chondrichthyans or a differential function of a novel GLP remains to be fully elucidated. [Abstract copyright: Copyright © 2024 Elsevier Inc. All rights reserved.]

KW - Intermediary metabolism

KW - Liver

KW - Elasmobranch

KW - Ketones

KW - Glucagon-like peptide

KW - Spiral Valve

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ER -

The chondrichthyan glucagon-like peptide 3 regulates hepatic ketone metabolism in the Pacific spiny dogfish Squalus suckleyi

Abstract

Bibliographical note

Data Access Statement

Funding

Keywords

UN SDGs

Access to Document

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