Kupffer Cells pp 121-127 | Cite as

An Obesogenic Dietary Mouse Model of Nonalcoholic Steatohepatitis

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


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.

Key words

NAFLD-NASH Mouse model Steatosis Inflammation Fibrosis Ballooning-NAS 



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


  1. 1.
    Diehl AM, Day C (2017) Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med 377(21):2063–2072. Scholar
  2. 2.
    Bellentani S (2017) The epidemiology of non-alcoholic fatty liver disease. Liver Int 37(Suppl 1):81–84. Scholar
  3. 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. Scholar
  4. 4.
    Issa D, Patel V, Sanyal AJ (2018) Future therapy for non-alcoholic fatty liver disease. Liver Int 38(Suppl 1):56–63. Scholar
  5. 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. Scholar
  6. 6.
    Larter CZ, Yeh MM (2008) Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol 23(11):1635–1648. Scholar
  7. 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. Scholar
  8. 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. Scholar
  9. 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. Scholar
  10. 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. Scholar
  11. 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. Scholar
  12. 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. Scholar
  13. 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).
  14. 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. Scholar

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

Authors and Affiliations

  1. 1.Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolic (CVRM), BioPharmaceuticals R&D, AstraZenecaGothenburgSweden
  2. 2.The Lundberg Laboratory for Diabetes ResearchUniversity of GothenburgGothenburgSweden
  3. 3.Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden

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