The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
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The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs. / Ipsen, D. H.; Agerskov, R. H.; Klaebel, J. H.; Lykkesfeldt, J.; Tveden-Nyborg, Pernille.
In: Scientific Reports, Vol. 11, 2955, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs
AU - Ipsen, D. H.
AU - Agerskov, R. H.
AU - Klaebel, J. H.
AU - Lykkesfeldt, J.
AU - Tveden-Nyborg, Pernille
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-82643-0
DO - 10.1038/s41598-021-82643-0
M3 - Journal article
C2 - 33536590
AN - SCOPUS:85100379426
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 2955
ER -
ID: 256891095