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Liver slice culture as a model for lipid metabolism in fish
Hepatic lipid metabolism is traditionally investigated in vitro using hepatocyte monocultures lacking the complex three-dimensional structure and interacting cell types essential liver function. Precision cut liver slice (PCLS) culture represents an alternative in vitro system, which benefits from r...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753922/ https://www.ncbi.nlm.nih.gov/pubmed/31576253 http://dx.doi.org/10.7717/peerj.7732 |
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author | Harvey, Thomas N. Sandve, Simen R. Jin, Yang Vik, Jon Olav Torgersen, Jacob S. |
author_facet | Harvey, Thomas N. Sandve, Simen R. Jin, Yang Vik, Jon Olav Torgersen, Jacob S. |
author_sort | Harvey, Thomas N. |
collection | PubMed |
description | Hepatic lipid metabolism is traditionally investigated in vitro using hepatocyte monocultures lacking the complex three-dimensional structure and interacting cell types essential liver function. Precision cut liver slice (PCLS) culture represents an alternative in vitro system, which benefits from retention of tissue architecture. Here, we present the first comprehensive evaluation of the PCLS method in fish (Atlantic salmon, Salmo salar L.) and validate it in the context of lipid metabolism using feeding trials, extensive transcriptomic data, and fatty acid measurements. We observe an initial period of post-slicing global transcriptome adjustment, which plateaued after 3 days in major metabolic pathways and stabilized through 9 days. PCLS fed alpha-linolenic acid (ALA) and insulin responded in a liver-like manner, increasing lipid biosynthesis gene expression. We identify interactions between insulin and ALA, where two PUFA biosynthesis genes that were induced by insulin or ALA alone, were highly down-regulated when insulin and ALA were combined. We also find that transcriptomic profiles of liver slices are exceedingly more similar to whole liver than hepatocyte monocultures, both for lipid metabolism and liver marker genes. PCLS culture opens new avenues for high throughput experimentation on the effect of “novel feed composition” and represent a promising new strategy for studying genotype-specific molecular features of metabolism. |
format | Online Article Text |
id | pubmed-6753922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67539222019-10-01 Liver slice culture as a model for lipid metabolism in fish Harvey, Thomas N. Sandve, Simen R. Jin, Yang Vik, Jon Olav Torgersen, Jacob S. PeerJ Aquaculture, Fisheries and Fish Science Hepatic lipid metabolism is traditionally investigated in vitro using hepatocyte monocultures lacking the complex three-dimensional structure and interacting cell types essential liver function. Precision cut liver slice (PCLS) culture represents an alternative in vitro system, which benefits from retention of tissue architecture. Here, we present the first comprehensive evaluation of the PCLS method in fish (Atlantic salmon, Salmo salar L.) and validate it in the context of lipid metabolism using feeding trials, extensive transcriptomic data, and fatty acid measurements. We observe an initial period of post-slicing global transcriptome adjustment, which plateaued after 3 days in major metabolic pathways and stabilized through 9 days. PCLS fed alpha-linolenic acid (ALA) and insulin responded in a liver-like manner, increasing lipid biosynthesis gene expression. We identify interactions between insulin and ALA, where two PUFA biosynthesis genes that were induced by insulin or ALA alone, were highly down-regulated when insulin and ALA were combined. We also find that transcriptomic profiles of liver slices are exceedingly more similar to whole liver than hepatocyte monocultures, both for lipid metabolism and liver marker genes. PCLS culture opens new avenues for high throughput experimentation on the effect of “novel feed composition” and represent a promising new strategy for studying genotype-specific molecular features of metabolism. PeerJ Inc. 2019-09-17 /pmc/articles/PMC6753922/ /pubmed/31576253 http://dx.doi.org/10.7717/peerj.7732 Text en © 2019 Harvey et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Aquaculture, Fisheries and Fish Science Harvey, Thomas N. Sandve, Simen R. Jin, Yang Vik, Jon Olav Torgersen, Jacob S. Liver slice culture as a model for lipid metabolism in fish |
title | Liver slice culture as a model for lipid metabolism in fish |
title_full | Liver slice culture as a model for lipid metabolism in fish |
title_fullStr | Liver slice culture as a model for lipid metabolism in fish |
title_full_unstemmed | Liver slice culture as a model for lipid metabolism in fish |
title_short | Liver slice culture as a model for lipid metabolism in fish |
title_sort | liver slice culture as a model for lipid metabolism in fish |
topic | Aquaculture, Fisheries and Fish Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753922/ https://www.ncbi.nlm.nih.gov/pubmed/31576253 http://dx.doi.org/10.7717/peerj.7732 |
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