The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs

Abstract Variability in disease development due to differences in strains and breeders constitutes a substantial challenge in preclinical research. However, the impact of the breeder on non-alcoholic steatohepatitis (NASH) is not yet fully elucidated. This retrospective study investigates NASH devel...

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Autores principales:	D. H. Ipsen, R. H. Agerskov, J. H. Klaebel, J. Lykkesfeldt, Pernille Tveden-Nyborg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e660e685d77b457cad45b3831fef5631
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spelling	oai:doaj.org-article:e660e685d77b457cad45b3831fef56312021-12-02T14:06:25ZThe development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs10.1038/s41598-021-82643-02045-2322https://doaj.org/article/e660e685d77b457cad45b3831fef56312021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82643-0https://doaj.org/toc/2045-2322Abstract Variability in disease development due to differences in strains and breeders constitutes a substantial challenge in preclinical research. However, the impact of the breeder on non-alcoholic steatohepatitis (NASH) is not yet fully elucidated. This retrospective study investigates NASH development in guinea pigs from Charles River or Envigo fed a high fat diet (20% fat, 15% sucrose, 0.35% cholesterol) for 16 or 24/25 weeks. Charles River animals displayed more severe NASH, with higher steatosis (p < 0.05 at week 16), inflammation (p < 0.05 at both week), fibrosis (p < 0.05 at week 16) and disease activity (p < 0.05 at both weeks). Accordingly, alanine and aspartate aminotransferase were increased at week 24/25 (p < 0.01). Hepatic expression of inflammatory (Ccl2, Cxcl8) and fibrotic (Pdgf, Serpine1, Col1a1) genes was also increased (p < 0.05). Differences were observed in healthy chow (4% fat, 0% sucrose, 0% cholesterol) fed animals: Envigo animals displayed higher relative liver weights (p < 0.01 at both weeks), liver cholesterol (p < 0.0001 at week 24/25) and aspartate aminotransferase (p < 0.05 at week 16), but lower levels of alkaline phosphatase (p < 0.0001 at week 24/25). These findings accentuates the importance of the breeder and its effect on NASH development and severity. Consequently, this may affect reproducibility, study comparison and limit the potential of developing novel therapies.D. H. IpsenR. H. AgerskovJ. H. KlaebelJ. LykkesfeldtPernille Tveden-NyborgNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q D. H. Ipsen R. H. Agerskov J. H. Klaebel J. Lykkesfeldt Pernille Tveden-Nyborg The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
description	Abstract Variability in disease development due to differences in strains and breeders constitutes a substantial challenge in preclinical research. However, the impact of the breeder on non-alcoholic steatohepatitis (NASH) is not yet fully elucidated. This retrospective study investigates NASH development in guinea pigs from Charles River or Envigo fed a high fat diet (20% fat, 15% sucrose, 0.35% cholesterol) for 16 or 24/25 weeks. Charles River animals displayed more severe NASH, with higher steatosis (p < 0.05 at week 16), inflammation (p < 0.05 at both week), fibrosis (p < 0.05 at week 16) and disease activity (p < 0.05 at both weeks). Accordingly, alanine and aspartate aminotransferase were increased at week 24/25 (p < 0.01). Hepatic expression of inflammatory (Ccl2, Cxcl8) and fibrotic (Pdgf, Serpine1, Col1a1) genes was also increased (p < 0.05). Differences were observed in healthy chow (4% fat, 0% sucrose, 0% cholesterol) fed animals: Envigo animals displayed higher relative liver weights (p < 0.01 at both weeks), liver cholesterol (p < 0.0001 at week 24/25) and aspartate aminotransferase (p < 0.05 at week 16), but lower levels of alkaline phosphatase (p < 0.0001 at week 24/25). These findings accentuates the importance of the breeder and its effect on NASH development and severity. Consequently, this may affect reproducibility, study comparison and limit the potential of developing novel therapies.
format	article
author	D. H. Ipsen R. H. Agerskov J. H. Klaebel J. Lykkesfeldt Pernille Tveden-Nyborg
author_facet	D. H. Ipsen R. H. Agerskov J. H. Klaebel J. Lykkesfeldt Pernille Tveden-Nyborg
author_sort	D. H. Ipsen
title	The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
title_short	The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
title_full	The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
title_fullStr	The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
title_full_unstemmed	The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
title_sort	development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e660e685d77b457cad45b3831fef5631
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The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs

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