An animal model for the juvenile non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Veronica Marin, Natalia Rosso, Matteo Dal Ben, Alan Raseni, Manuela Boschelle, Cristina Degrassi, Ivana Nemeckova, Petr Nachtigal, Claudio Avellini, Claudio Tiribelli, Silvia Gazzin

Research output: Contribution to journalArticle

Abstract

Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

Original languageEnglish
Article numbere0158817
JournalPLoS One
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Marin, V., Rosso, N., Dal Ben, M., Raseni, A., Boschelle, M., Degrassi, C., Nemeckova, I., Nachtigal, P., Avellini, C., Tiribelli, C., & Gazzin, S. (2016). An animal model for the juvenile non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. PLoS One, 11(7), [e0158817]. https://doi.org/10.1371/journal.pone.0158817