A Systematic Review of Animal Models of NAFLD Finds High-Fat, High-Fructose Diets Most Closely Resemble Human NAFLD.
Animals
Animals, Genetically Modified
Cholesterol, Dietary
Diet
Diet, High-Fat
Dietary Sucrose
Dietary Sugars
Disease Models, Animal
Dyslipidemias
/ genetics
Female
Fructose
Humans
Liver
/ pathology
Male
Metabolic Syndrome
/ genetics
Mice
Non-alcoholic Fatty Liver Disease
/ genetics
Obesity
/ genetics
Rats
Reproducibility of Results
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
29
04
2021
received:
23
03
2021
accepted:
04
05
2021
pubmed:
12
5
2021
medline:
11
1
2022
entrez:
11
5
2021
Statut:
ppublish
Résumé
Animal models of human disease are a key component of translational hepatology research, yet there is no consensus on which model is optimal for NAFLD. We generated a database of 3,920 rodent models of NAFLD. Study designs were highly heterogeneous, and therefore, few models had been cited more than once. Analysis of genetic models supported the current evidence for the role of adipose dysfunction and suggested a role for innate immunity in the progression of NAFLD. We identified that high-fat, high-fructose diets most closely recapitulate the human phenotype of NAFLD. There was substantial variability in the nomenclature of animal models: a consensus on terminology of specialist diets is needed. More broadly, this analysis demonstrates the variability in preclinical study design, which has wider implications for the reproducibility of in vivo experiments both in the field of hepatology and beyond. This systematic analysis provides a framework for phenotypic assessment of NAFLD models and highlights the need for increased standardization and replication.
Sections du résumé
BACKGROUND AND AIMS
Animal models of human disease are a key component of translational hepatology research, yet there is no consensus on which model is optimal for NAFLD.
APPROACH AND RESULTS
We generated a database of 3,920 rodent models of NAFLD. Study designs were highly heterogeneous, and therefore, few models had been cited more than once. Analysis of genetic models supported the current evidence for the role of adipose dysfunction and suggested a role for innate immunity in the progression of NAFLD. We identified that high-fat, high-fructose diets most closely recapitulate the human phenotype of NAFLD. There was substantial variability in the nomenclature of animal models: a consensus on terminology of specialist diets is needed. More broadly, this analysis demonstrates the variability in preclinical study design, which has wider implications for the reproducibility of in vivo experiments both in the field of hepatology and beyond.
CONCLUSIONS
This systematic analysis provides a framework for phenotypic assessment of NAFLD models and highlights the need for increased standardization and replication.
Substances chimiques
Cholesterol, Dietary
0
Dietary Sucrose
0
Dietary Sugars
0
Fructose
30237-26-4
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1884-1901Subventions
Organisme : Wellcome Trust
ID : 216329/Z/19/Z
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
Références
Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med 2017;377:2063-2072.
Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2015;149:389-397.e10.
Paik JM, Golabi P, Younossi Y, Srishord M, Mishra A, Younossi ZM. The growing burden of disability related to nonalcoholic fatty liver disease: data from the global burden of disease 2007-2017. Hepatol Commun 2020;4:1769-1780.
Liu Z, Zhang Y, Graham S, Wang X, Cai D, Huang M, et al. Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping. J Hepatol 2020;73:263-276.
Eslam M, Sanyal AJ, George J, Sanyal A, Neuschwander-Tetri B, Tiribelli C, et al. International consensus panel. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158:1999-2014.e1.
Luukkonen PK, Zhou Y, Sädevirta S, Leivonen M, Arola J, Orešič M, et al. Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. J Hepatol 2016;64:1167-1175.
Mann JP, Pietzner M, Wittemans LB, Rolfe EDL, Kerrison ND, Imamura F, et al. Insights into genetic variants associated with NASH-fibrosis from metabolite profiling. Hum Mol Genet 2020;29:3451-3463.
Brunt EM, Kleiner DE, Carpenter DH, Rinella M, Harrison SA, Loomba R, et al. NAFLD: reporting histologic findings in clinical practice. Hepatology 2021;73:2028-2038.
Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2011;8:35-44.
Febbraio MA, Reibe S, Shalapour S, Ooi GJ, Watt MJ, Karin M. Preclinical models for studying NASH-driven HCC: how useful are they? Cell Metab 2019;29:18-26.
Hunter H, de Gracia Hahn D, Duret A, Im YR, Cheah Q, Dong J, et al. Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver. Elife 2020;9:e56573.
von Herrath M, Pagni PP, Grove K, Christoffersson G, Tang-Christensen M, Karlsen AE, et al. Case reports of pre-clinical replication studies in metabolism and diabetes. Cell Metab 2019;29:795-802.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016;5:210.
Eppig JT, Smith CL, Blake JA, Ringwald M, Kadin JA, Richardson JE, et al. Mouse Genome Informatics (MGI): resources for mining mouse genetic, genomic, and biological data in support of primary and translational research. In: Schughart K, Williams RW, eds. Systems Genetics: Methods and Protocols. New York, NY: Springer; 2017:47-73.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-1321.
Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 2016;44:W90-W97.
R Core Team. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2019.
Harrer M, Cuijpers P, Furukawa TA, Ebert DD. Doing Meta-Analysis in R: A Hands-on Guide. Erlangen, Germany: PROTECT Lab; 2019.
Giles DA, Moreno-Fernandez ME, Stankiewicz TE, Graspeuntner S, Cappelletti M, Wu D, et al. Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling. Nat Med 2017;23:829-838.
Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol 2016;65:579-588.
Cazanave S, Podtelezhnikov A, Jensen K, Seneshaw M, Kumar DP, Min H-K, et al. The transcriptomic signature of disease development and progression of nonalcoholic fatty liver disease. Sci Rep 2017;7:17193.
Dowman JK, Hopkins LJ, Reynolds GM, Nikolaou N, Armstrong MJ, Shaw JC, et al. Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle. Am J Pathol 2014;184:1550-1561.
Tsuchida T, Lee YA, Fujiwara N, Ybanez M, Allen B, Martins S, et al. A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J Hepatol 2018;69:385-395.
Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, et al. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-clinicopathologic correlation from the Nonalcoholic Steatohepatitis Clinical Research Network. Hepatology 2009;49:809-820.
Teufel A, Itzel T, Erhart W, Brosch M, Wang XY, Kim YO, et al. Comparison of gene expression patterns between mouse models of nonalcoholic fatty liver disease and liver tissues from patients. Gastroenterology 2016;151:513-525.e0.
Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol 2020;18:e3000410.
Eilert ML, Dragstedt LR. Lipotropic action of lipocaic; a study of the effect of oral and parenteral lipocaic and oral inositol on the dietary fatty liver of the white rat. Am J Physiol 1946;147:346-351.
Nevzorova YA, Boyer-Diaz Z, Cubero FJ, Gracia-Sancho J. Animal models for liver disease-a practical approach for translational research. J Hepatol 2020;73:423-440.
Jaskiewicz K, Rossouw JE, Kritchevsky D, van Rensburg SJ, Fincham JE, Woodroof CW. The influence of diet and dimethylhydrazine on the small and large intestine of vervet monkeys. Br J Exp Pathol 1986;67:361-369.
Baker SP, Ogden E, Riddle JW. Serological detection of abnormal concentrations of serum lipoproteins in dogs on cholesterol-thiouracil atherogenic diets. Proc Soc Exp Biol Med 1953;82:119-122.
Duarte JAG, Carvalho F, Pearson M, Horton JD, Browning JD, Jones JG, et al. A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice. J Lipid Res 2014;55:2541-2553.
Castro RE, Diehl AM. Towards a definite mouse model of NAFLD. J Hepatol 2018;69:272-274.
Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018;24:908-922.
Zhao S, Jang C, Liu J, Uehara K, Gilbert M, Izzo L, et al. Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature 2020;579:586-591.
Jang C, Wada S, Yang S, Gosis B, Zeng X, Zhang Z, et al. The small intestine shields the liver from fructose-induced steatosis. Nat Metab 2020;2:586-593.
Todoric J, Di Caro G, Reibe S, Henstridge DC, Green CR, Vrbanac A, et al. Fructose stimulated de novo lipogenesis is promoted by inflammation. Nat Metab 2020;2:1034-1045.
Mann JP, Savage DB. What lipodystrophies teach us about the metabolic syndrome. J Clin Invest 2019;130:4009-4021.
Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Lauren J, Palmer CD, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011;7:e1001324.
Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, et al. Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis. J Hepatol 2020;73:241-251.
Emdin CA, Haas ME, Khera AV, Aragam K, Chaffin M, Klarin D, et al. A missense variant in mitochondrial amidoxime reducing component 1 gene and protection against liver disease. PLoS Genet 2020;16:e1008629.
Cai B, Dongiovanni P, Corey KE, Wang X, Shmarakov IO, Zheng ZE, et al. Macrophage MerTK promotes liver fibrosis in nonalcoholic steatohepatitis. Cell Metab 2020;31:406-421.e7.
Eslam M, Hashem AM, Leung R, Romero-Gomez M, Berg T, Dore GJ, et al. Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease. Nat Commun 2015;6:6422.
Patin E, Kutalik Z, Guergnon J, Bibert S, Nalpas B, Jouanguy E, et al. Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection. Gastroenterology 2012;143:1244-1252.e12.
Namjou B, Lingren T, Huang Y, Parameswaran S, Cobb BL, Stanaway IB, et al. GWAS and enrichment analyses of non-alcoholic fatty liver disease identify new trait-associated genes and pathways across eMERGE Network. BMC Med 2019;17:135.
Harrison SA, Wong VW, Okanoue T, Bzowej N, Vuppalanchi R, Younes Z, et al. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: results from randomized phase III STELLAR trials. J Hepatol 2020;73:26-39.
Chella Krishnan K, Kurt Z, Barrere-Cain R, Sabir S, Das A, Floyd R, et al. Integration of multi-omics data from mouse diversity panel highlights mitochondrial dysfunction in non-alcoholic fatty liver disease. Cell Systems 2018;6:103-115.e7.
Norheim F, Bjellaas T, Hui ST, Chella Krishnan K, Lee J, Gupta S, et al. Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR. J Lipid Res 2018;59:1164-1174.
Hui ST, Parks BW, Org E, Norheim F, Che N, Pan C, et al. The genetic architecture of NAFLD among inbred strains of mice. Elife 2015;4:e05607.
Hui ST, Kurt Z, Tuominen I, Norheim F, Davis RC, Pan C, et al. The genetic architecture of diet-induced hepatic fibrosis in mice. Hepatology 2018;68:2182-2196.
Lee G, You HJ, Bajaj JS, Joo SK, Yu J, Park S, et al. Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD. Nat Commun 2020;11:4982.