NASH-inducing Diets in Göttingen Minipigs

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NASH-inducing Diets in Göttingen Minipigs. / Pedersen, Henrik D.; Galsgaard, Elisabeth D.; Christoffersen, Berit; Cirera, Susanna; Holst, Dorte; Fredholm, Merete; Latta, Markus.

I: Journal of Clinical and Experimental Hepatology, Bind 10, Nr. 3, 2020, s. 211-221.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Pedersen, HD, Galsgaard, ED, Christoffersen, B, Cirera, S, Holst, D, Fredholm, M & Latta, M 2020, 'NASH-inducing Diets in Göttingen Minipigs', Journal of Clinical and Experimental Hepatology, bind 10, nr. 3, s. 211-221. https://doi.org/10.1016/j.jceh.2019.09.004

APA

Pedersen, H. D., Galsgaard, E. D., Christoffersen, B., Cirera, S., Holst, D., Fredholm, M., & Latta, M. (2020). NASH-inducing Diets in Göttingen Minipigs. Journal of Clinical and Experimental Hepatology, 10(3), 211-221. https://doi.org/10.1016/j.jceh.2019.09.004

Vancouver

Pedersen HD, Galsgaard ED, Christoffersen B, Cirera S, Holst D, Fredholm M o.a. NASH-inducing Diets in Göttingen Minipigs. Journal of Clinical and Experimental Hepatology. 2020;10(3):211-221. https://doi.org/10.1016/j.jceh.2019.09.004

Author

Pedersen, Henrik D. ; Galsgaard, Elisabeth D. ; Christoffersen, Berit ; Cirera, Susanna ; Holst, Dorte ; Fredholm, Merete ; Latta, Markus. / NASH-inducing Diets in Göttingen Minipigs. I: Journal of Clinical and Experimental Hepatology. 2020 ; Bind 10, Nr. 3. s. 211-221.

Bibtex

@article{2c5c809e44864b94a1f4811c5a30d34d,
title = "NASH-inducing Diets in G{\"o}ttingen Minipigs",
abstract = "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 G{\"o}ttingen Minipigs. Methods: Castrated male G{\"o}ttingen 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: G{\"o}ttingen 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.",
keywords = "Animal model, Choline, Fatty liver, Fibrosis, Porcine",
author = "Pedersen, {Henrik D.} and Galsgaard, {Elisabeth D.} and Berit Christoffersen and Susanna Cirera and Dorte Holst and Merete Fredholm and Markus Latta",
year = "2020",
doi = "10.1016/j.jceh.2019.09.004",
language = "English",
volume = "10",
pages = "211--221",
journal = "Journal of Clinical and Experimental Hepatology",
issn = "0973-6883",
publisher = "Elsevier Health Sciences",
number = "3",

}

RIS

TY - JOUR

T1 - NASH-inducing Diets in Göttingen Minipigs

AU - Pedersen, Henrik D.

AU - Galsgaard, Elisabeth D.

AU - Christoffersen, Berit

AU - Cirera, Susanna

AU - Holst, Dorte

AU - Fredholm, Merete

AU - Latta, Markus

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Animal model

KW - Choline

KW - Fatty liver

KW - Fibrosis

KW - Porcine

U2 - 10.1016/j.jceh.2019.09.004

DO - 10.1016/j.jceh.2019.09.004

M3 - Journal article

C2 - 32405177

AN - SCOPUS:85073719613

VL - 10

SP - 211

EP - 221

JO - Journal of Clinical and Experimental Hepatology

JF - Journal of Clinical and Experimental Hepatology

SN - 0973-6883

IS - 3

ER -

ID: 229442422