Studying non-alcoholic fatty liver disease: The ins and outs of in vivo, ex vivo and in vitro human models

Charlotte J. Green, Siôn A. Parry, Pippa J. Gunn, Carlo D.L. Ceresa, Fredrik Rosqvist, Marie Eve Piché, Leanne Hodson*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Determining the pathogenesis and pathophysiology of human NAFLD will allow for evidence-based prevention strategies, and more targeted mechanistic investigations. Various in vivo, ex situ and in vitro models may be utilised to study NAFLD; but all come with their own specific caveats. Here, we review the human-based models and discuss their advantages and limitations in regards to studying the development and progression of NAFLD. Overall, in vivo whole-body human studies are advantageous in that they allow for investigation within the physiological setting, however, limited accessibility to the liver makes direct investigations challenging. Non-invasive imaging techniques are able to somewhat overcome this challenge, whilst the use of stable-isotope tracers enables mechanistic insight to be obtained. Recent technological advances (i.e. normothermic machine perfusion) have opened new opportunities to investigate whole-organ metabolism, thus ex situ livers can be investigated directly. Therefore, investigations that cannot be performed in vivo in humans have the potential to be undertaken. In vitro models offer the ability to perform investigations at a cellular level, aiding in elucidating the molecular mechanisms of NAFLD. However, a number of current models do not closely resemble the human condition and work is ongoing to optimise culturing parameters in order to recapitulate this. In summary, no single model currently provides insight into the development, pathophysiology and progression across the NAFLD spectrum, each experimental model has limitations, which need to be taken into consideration to ensure appropriate conclusions and extrapolation of findings are made.

Original languageEnglish
Article number20180038
JournalHormone Molecular Biology and Clinical Investigation
Issue number1
Early online date11 Aug 2018
Publication statusPublished - Mar 2020

Bibliographical note

Funding Information:
LH is a British Heart Foundation Senior Research Fellow in Basic Science. FR is supported by Henning and Johan Throne-Holsts Foundation, Swedish Society for Medical Research, Swedish Society of Medicine and The Foundation Blanceflor. M-E P is supported by postdoctoral training grants from Fonds de Recherche du Québec-Santé and the Heart and Lung Institute Foundation.


  • fatty acids
  • human
  • liver
  • steatosis
  • VLDL


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