Skip to main content

An Obesogenic Dietary Mouse Model of Nonalcoholic Steatohepatitis

  • Protocol
  • First Online:
Kupffer Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2164))

  • 1915 Accesses

Abstract

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), characterized by steatosis (fat within the liver), inflammation, and fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Despite the high prevalence, there are currently no approved NASH drug treatments, which urges a faster development of new therapies to address this high unmet medical need. Drug development is facilitated by having reliable and translatable preclinical NASH models. Obesogenic dietary models recapitulate better the natural progression of NASH, with overnutrition and sedentary lifestyle being the main causes. Here we describe the use of a modified version of a diet-induced NASH model, known as the Amylin NASH diet model (AMLN-diet), particularly in the leptin-deficient Lepob/Lepob (ob/ob) mice.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Diehl AM, Day C (2017) Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med 377(21):2063–2072. https://doi.org/10.1056/NEJMra1503519

    Article  CAS  PubMed  Google Scholar 

  2. Bellentani S (2017) The epidemiology of non-alcoholic fatty liver disease. Liver Int 37(Suppl 1):81–84. https://doi.org/10.1111/liv.13299

    Article  PubMed  Google Scholar 

  3. Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, Colombo M, Craxi A, Crespo J, Day CP, Eguchi Y, Geier A, Kondili LA, Kroy DC, Lazarus JV, Loomba R, Manns MP, Marchesini G, Nakajima A, Negro F, Petta S, Ratziu V, Romero-Gomez M, Sanyal A, Schattenberg JM, Tacke F, Tanaka J, Trautwein C, Wei L, Zeuzem S, Razavi H (2018) Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol 69(4):896–904. https://doi.org/10.1016/j.jhep.2018.05.036

    Article  PubMed  Google Scholar 

  4. Issa D, Patel V, Sanyal AJ (2018) Future therapy for non-alcoholic fatty liver disease. Liver Int 38(Suppl 1):56–63. https://doi.org/10.1111/liv.13676

    Article  PubMed  Google Scholar 

  5. Hansen HH, Feigh M, Veidal SS, Rigbolt KT, Vrang N, Fosgerau K (2017) Mouse models of nonalcoholic steatohepatitis in preclinical drug development. Drug Discov Today 22(11):1707–1718. https://doi.org/10.1016/j.drudis.2017.06.007

    Article  CAS  PubMed  Google Scholar 

  6. Larter CZ, Yeh MM (2008) Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol 23(11):1635–1648. https://doi.org/10.1111/j.1440-1746.2008.05543.x

    Article  PubMed  Google Scholar 

  7. Trevaskis JL, Griffin PS, Wittmer C, Neuschwander-Tetri BA, Brunt EM, Dolman CS, Erickson MR, Napora J, Parkes DG, Roth JD (2012) Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol 302(8):G762–G772. https://doi.org/10.1152/ajpgi.00476.2011

    Article  CAS  PubMed  Google Scholar 

  8. Clapper JR, Hendricks MD, Gu G, Wittmer C, Dolman CS, Herich J, Athanacio J, Villescaz C, Ghosh SS, Heilig JS, Lowe C, Roth JD (2013) Diet-induced mouse model of fatty liver disease and nonalcoholic steatohepatitis reflecting clinical disease progression and methods of assessment. Am J Physiol Gastrointest Liver Physiol 305(7):G483–G495. https://doi.org/10.1152/ajpgi.00079.2013

    Article  CAS  PubMed  Google Scholar 

  9. Kristiansen MN, Veidal SS, Rigbolt KT, Tolbol KS, Roth JD, Jelsing J, Vrang N, Feigh M (2016) Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy. World J Hepatol 8(16):673–684. https://doi.org/10.4254/wjh.v8.i16.673

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tolbol KS, Kristiansen MN, Hansen HH, Veidal SS, Rigbolt KT, Gillum MP, Jelsing J, Vrang N, Feigh M (2018) Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis. World J Gastroenterol 24(2):179–194. https://doi.org/10.3748/wjg.v24.i2.179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Boland ML, Oro D, Tolbol KS, Thrane ST, Nielsen JC, Cohen TS, Tabor DE, Fernandes F, Tovchigrechko A, Veidal SS, Warrener P, Sellman BR, Jelsing J, Feigh M, Vrang N, Trevaskis JL, Hansen HH (2019) Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: impact of dietary fat source. World J Gastroenterol 25(33):4904–4920. https://doi.org/10.3748/wjg.v25.i33.4904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Linden D, Ahnmark A, Pingitore P, Ciociola E, Ahlstedt I, Andreasson AC, Sasidharan K, Madeyski-Bengtson K, Zurek M, Mancina RM, Lindblom A, Bjursell M, Bottcher G, Stahlman M, Bohlooly YM, Haynes WG, Carlsson B, Graham M, Lee R, Murray S, Valenti L, Bhanot S, Akerblad P, Romeo S (2019) Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice. Mol Metab 22:49–61. https://doi.org/10.1016/j.molmet.2019.01.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Oldham S, Rivera C, Boland ML, Trevaskis JL (2019) Incorporation of a survivable liver biopsy procedure in mice to assess non-alcoholic steatohepatitis (NASH) resolution. J Vis Exp (146). https://doi.org/10.3791/59130

  14. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ, Nonalcoholic Steatohepatitis Clinical Research Network (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6):1313–1321. https://doi.org/10.1002/hep.20701

    Article  Google Scholar 

Download references

Disclosure

The authors are AstraZeneca employees and declare no competing interests related to this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bader Zarrouki .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Zarrouki, B., Boucher, J. (2020). An Obesogenic Dietary Mouse Model of Nonalcoholic Steatohepatitis. In: Aouadi, M., Azzimato, V. (eds) Kupffer Cells. Methods in Molecular Biology, vol 2164. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0704-6_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0704-6_13

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0703-9

  • Online ISBN: 978-1-0716-0704-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics