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NASH-inducing Diets in Göttingen Minipigs

BACKGROUND: Owing to the human-like physiology, a minipig model of nonalcoholic steatohepatitis (NASH) could be valuable. Pigs, however, rarely develop substantial hepatic steatosis, even when fed diets with high fat, fructose, and cholesterol (FFC) content. The potential of choline-deficient, amino...

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Autores principales: Pedersen, Henrik D., Galsgaard, Elisabeth D., Christoffersen, Berit Ø., Cirera, Susanna, Holst, Dorte, Fredholm, Merete, Latta, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212300/
https://www.ncbi.nlm.nih.gov/pubmed/32405177
http://dx.doi.org/10.1016/j.jceh.2019.09.004
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author Pedersen, Henrik D.
Galsgaard, Elisabeth D.
Christoffersen, Berit Ø.
Cirera, Susanna
Holst, Dorte
Fredholm, Merete
Latta, Markus
author_facet Pedersen, Henrik D.
Galsgaard, Elisabeth D.
Christoffersen, Berit Ø.
Cirera, Susanna
Holst, Dorte
Fredholm, Merete
Latta, Markus
author_sort Pedersen, Henrik D.
collection PubMed
description BACKGROUND: Owing to the human-like physiology, a minipig model of nonalcoholic steatohepatitis (NASH) could be valuable. Pigs, however, rarely develop substantial hepatic steatosis, even when fed diets with high fat, fructose, and cholesterol (FFC) content. The potential of choline-deficient, amino acid–defined high-fat diets (CDAHFD) was therefore evaluated in Göttingen Minipigs. METHODS: Castrated male Göttingen Minipigs were fed either chow (n = 5) or one of the three NASH diets: FFC (n = 5), CDAHFD with sucrose (CDAHFD-S; n = 4), or fructose (CDAHFD-F; n = 4) for 8 weeks. Liver and blood samples were collected after 2 weeks and at termination. RESULTS: Compared with chow, the body weight was higher after FFC (9.8 ± 0.4 versus 8.5 ± 1.2 kg; mean ± SD) and less after CDAHFD-S (6.4 ± 0.8 kg) and CDAHFD-F (6.9 ± 0.8 kg). Liver weight per kg body weight was significantly increased in all 3 NASH groups (FFC 2.1 times; and both CDAHFD diets 3.1 times). Histologically, pronounced macrovesicular steatosis developed only in the CDAHFD groups. Inflammation was present in all three NASH groups. In the CDAHFD groups, inflammatory cells formed crown-like structures around steatotic hepatocytes. Sirius red staining revealed mild fibrosis in the two CDAHFD groups with the fibrotic potential being further supported by immunohistochemical staining for activated stellate cells and gene expression analyses. No noticeable differences were found between CDAHFD-S and CDAHFD-F. CONCLUSIONS: Göttingen Minipigs fed CDAHFD developed pronounced steatosis with inflammation around steatotic hepatocytes and incipient fibrosis, thereby showing potential as a model for human NASH. Further studies are needed to investigate the period needed for marked fibrosis to develop.
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spelling pubmed-72123002021-05-01 NASH-inducing Diets in Göttingen Minipigs Pedersen, Henrik D. Galsgaard, Elisabeth D. Christoffersen, Berit Ø. Cirera, Susanna Holst, Dorte Fredholm, Merete Latta, Markus J Clin Exp Hepatol Original Article BACKGROUND: Owing to the human-like physiology, a minipig model of nonalcoholic steatohepatitis (NASH) could be valuable. Pigs, however, rarely develop substantial hepatic steatosis, even when fed diets with high fat, fructose, and cholesterol (FFC) content. The potential of choline-deficient, amino acid–defined high-fat diets (CDAHFD) was therefore evaluated in Göttingen Minipigs. METHODS: Castrated male Göttingen Minipigs were fed either chow (n = 5) or one of the three NASH diets: FFC (n = 5), CDAHFD with sucrose (CDAHFD-S; n = 4), or fructose (CDAHFD-F; n = 4) for 8 weeks. Liver and blood samples were collected after 2 weeks and at termination. RESULTS: Compared with chow, the body weight was higher after FFC (9.8 ± 0.4 versus 8.5 ± 1.2 kg; mean ± SD) and less after CDAHFD-S (6.4 ± 0.8 kg) and CDAHFD-F (6.9 ± 0.8 kg). Liver weight per kg body weight was significantly increased in all 3 NASH groups (FFC 2.1 times; and both CDAHFD diets 3.1 times). Histologically, pronounced macrovesicular steatosis developed only in the CDAHFD groups. Inflammation was present in all three NASH groups. In the CDAHFD groups, inflammatory cells formed crown-like structures around steatotic hepatocytes. Sirius red staining revealed mild fibrosis in the two CDAHFD groups with the fibrotic potential being further supported by immunohistochemical staining for activated stellate cells and gene expression analyses. No noticeable differences were found between CDAHFD-S and CDAHFD-F. CONCLUSIONS: Göttingen Minipigs fed CDAHFD developed pronounced steatosis with inflammation around steatotic hepatocytes and incipient fibrosis, thereby showing potential as a model for human NASH. Further studies are needed to investigate the period needed for marked fibrosis to develop. Elsevier 2020 2019-09-21 /pmc/articles/PMC7212300/ /pubmed/32405177 http://dx.doi.org/10.1016/j.jceh.2019.09.004 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Pedersen, Henrik D.
Galsgaard, Elisabeth D.
Christoffersen, Berit Ø.
Cirera, Susanna
Holst, Dorte
Fredholm, Merete
Latta, Markus
NASH-inducing Diets in Göttingen Minipigs
title NASH-inducing Diets in Göttingen Minipigs
title_full NASH-inducing Diets in Göttingen Minipigs
title_fullStr NASH-inducing Diets in Göttingen Minipigs
title_full_unstemmed NASH-inducing Diets in Göttingen Minipigs
title_short NASH-inducing Diets in Göttingen Minipigs
title_sort nash-inducing diets in göttingen minipigs
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212300/
https://www.ncbi.nlm.nih.gov/pubmed/32405177
http://dx.doi.org/10.1016/j.jceh.2019.09.004
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