In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Dec 30

PMID 33374435

Citations 46

Authors

Pierre-Antoine Soret

Julie Magusto

Chantal Housset

Jeremie Gautheron

Affiliations

Soon will be listed here.

Abstract

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. Due to the spread of the obesity epidemic, NAFLD is becoming the most common chronic liver disease and one of the principal indications for liver transplantation. However, no pharmacological treatment is currently approved to prevent the outbreak of NASH, which leads to fibrosis and cirrhosis. Preclinical research is required to improve our knowledge of NAFLD physiopathology and to identify new therapeutic targets. In the present review, we summarize advances in NAFLD preclinical models from cellular models, including new bioengineered platforms, to in vivo models, with a particular focus on genetic and dietary mouse models. We aim to discuss the advantages and limits of these different models.

Citing Articles

Molecular Mechanisms of Phthalate-Induced Hepatic Injury and Amelioration by Plant-Based Principles.

Singh L, Pandey R, Siddiqi N, Sharma B Toxics. 2025; 13(1).

PMID: 39853030 PMC: 11768991. DOI: 10.3390/toxics13010032.

Impact of Post-Thaw Enrichment of Primary Human Hepatocytes on Steatosis, Inflammation, and Fibrosis in the TruVivo System.

Odanga J, Anderson S, Presnell S, LeCluyse E, Chen J, Weaver J Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770467 PMC: 11728523. DOI: 10.3390/ph17121624.

High-Throughput Formation of Pre-Vascularized hiPSC-Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting.

Fan H, Shang J, Li J, Yang B, Zhou D, Jiang S Adv Sci (Weinh). 2025; 12(8):e2407945.

PMID: 39755926 PMC: 11848576. DOI: 10.1002/advs.202407945.

Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.

Li X, Chen S, Shi Y, Wang Y, Wang X, Lin Q Front Pharmacol. 2025; 15:1464852.

PMID: 39744125 PMC: 11688200. DOI: 10.3389/fphar.2024.1464852.

Unlocking Therapeutic Potential: Camphorquinone's Role in Alleviating Non-Alcoholic Fatty Liver Disease via SIRT1/LKB1/AMPK Pathway Activation.

Maharajan N, Kim K, Vijayakumar K, Cho G Tissue Eng Regen Med. 2024; 22(1):129-144.

PMID: 39680356 PMC: 11712022. DOI: 10.1007/s13770-024-00684-8.

References

Klok M, Jakobsdottir S, Drent M . The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007; 8(1):21-34. DOI: 10.1111/j.1467-789X.2006.00270.x. View

Aoudjehane L, Gautheron J, Le Goff W, Goumard C, Gilaizeau J, Nget C . Novel defatting strategies reduce lipid accumulation in primary human culture models of liver steatosis. Dis Model Mech. 2020; 13(4). PMC: 7197711. DOI: 10.1242/dmm.042663. View

Wilkening S, Stahl F, Bader A . Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos. 2003; 31(8):1035-42. DOI: 10.1124/dmd.31.8.1035. View

Maciejewska D, Lukomska A, Dec K, Skonieczna-Zydecka K, Gutowska I, Skorka-Majewicz M . Diet-Induced Rat Model of Gradual Development of Non-Alcoholic Fatty Liver Disease (NAFLD) with Lipopolysaccharides (LPS) Secretion. Diagnostics (Basel). 2019; 9(4). PMC: 6963178. DOI: 10.3390/diagnostics9040205. View

Kim Y, Lee E, Shin K, Kim M, Pewzner-Jung Y, Lee Y . Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases. Exp Mol Med. 2019; 51(11):1-16. PMC: 6825147. DOI: 10.1038/s12276-019-0340-1. View

Suurmond C, Lasli S, van den Dolder F, Ung A, Kim H, Bandaru P . In Vitro Human Liver Model of Nonalcoholic Steatohepatitis by Coculturing Hepatocytes, Endothelial Cells, and Kupffer Cells. Adv Healthc Mater. 2019; 8(24):e1901379. DOI: 10.1002/adhm.201901379. View

Polyzos S, Kountouras J, Mantzoros C . Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism. 2014; 64(1):60-78. DOI: 10.1016/j.metabol.2014.10.012. View

Huaman Samanez C, Caron S, Briand O, Dehondt H, Duplan I, Kuipers F . The human hepatocyte cell lines IHH and HepaRG: models to study glucose, lipid and lipoprotein metabolism. Arch Physiol Biochem. 2012; 118(3):102-11. DOI: 10.3109/13813455.2012.683442. View

Lee S, Sung J . Gut-liver on a chip toward an in vitro model of hepatic steatosis. Biotechnol Bioeng. 2018; 115(11):2817-2827. DOI: 10.1002/bit.26793. View

10.

Lin Y, Ding D, Huang Q, Liu Q, Lu H, Lu Y . Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2017; 1862(9):869-882. DOI: 10.1016/j.bbalip.2017.05.001. View

11.

Ratziu V, Friedman S . Why Do So Many Nonalcoholic Steatohepatitis Trials Fail?. Gastroenterology. 2020; 165(1):5-10. DOI: 10.1053/j.gastro.2020.05.046. View

12.

Trak-Smayra V, Paradis V, Massart J, Nasser S, Jebara V, Fromenty B . Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet. Int J Exp Pathol. 2011; 92(6):413-21. PMC: 3248077. DOI: 10.1111/j.1365-2613.2011.00793.x. View

13.

Sanches S, Ramalho L, Augusto M, da Silva D, Ramalho F . Nonalcoholic Steatohepatitis: A Search for Factual Animal Models. Biomed Res Int. 2015; 2015:574832. PMC: 4433658. DOI: 10.1155/2015/574832. View

14.

Santhekadur P, Kumar D, Sanyal A . Preclinical models of non-alcoholic fatty liver disease. J Hepatol. 2017; 68(2):230-237. PMC: 5775040. DOI: 10.1016/j.jhep.2017.10.031. View

15.

Ramboer E, De Craene B, Kock J, Vanhaecke T, Berx G, Rogiers V . Strategies for immortalization of primary hepatocytes. J Hepatol. 2014; 61(4):925-43. PMC: 4169710. DOI: 10.1016/j.jhep.2014.05.046. View

16.

Schumacher-Petersen C, Christoffersen B, Kirk R, Ludvigsen T, Zois N, Pedersen H . Experimental non-alcoholic steatohepatitis in Göttingen Minipigs: consequences of high fat-fructose-cholesterol diet and diabetes. J Transl Med. 2019; 17(1):110. PMC: 6448276. DOI: 10.1186/s12967-019-1854-y. View

17.

Richert L, Alexandre E, Lloyd T, Orr S, Viollon-Abadie C, Patel R . Tissue collection, transport and isolation procedures required to optimize human hepatocyte isolation from waste liver surgical resections. A multilaboratory study. Liver Int. 2004; 24(4):371-8. DOI: 10.1111/j.1478-3231.2004.0930.x. View

18.

Green C, Pramfalk C, Morten K, Hodson L . From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations. Am J Physiol Endocrinol Metab. 2014; 308(1):E1-20. PMC: 4281685. DOI: 10.1152/ajpendo.00192.2014. View

19.

Winzell M, Ahren B . The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes. 2004; 53 Suppl 3:S215-9. DOI: 10.2337/diabetes.53.suppl_3.s215. View

20.

Younossi Z . Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2018; 70(3):531-544. DOI: 10.1016/j.jhep.2018.10.033. View