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Animal Models of Nonalcoholic Fatty Liver Disease

  • Chapter
Alcoholic and Non-Alcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, accompanying the rise in obesity and its related metabolic disorders. Though research in the field is vibrant, enormous gaps in knowledge still remain about its physiology, how to identify patients who are most susceptible for adverse outcomes, and the best therapeutic approach. It is difficult to study NAFLD in humans, since the disease evolves slowly and encompasses diverse liver phenotypes that are challenging to differentiate noninvasively. Steatosis is the most clinically benign NAFLD phenotype, while nonalcoholic steatohepatitis (NASH) has a much more variable prognosis that seems to depend upon the severity of hepatocyte injury and propensity for progressive fibrosis. NASH patients in whom fibrosis progresses to cirrhosis ultimately develop the worst liver-related outcomes because cirrhosis increases the risk for primary liver cancer, liver-related morbidity, and death from liver disease. Animal models that mimic the spectrum of human NAFLD pathology are crucial to overcome the challenges inherent in human NAFLD research so that knowledge about this disease can advance. There are many animal models for NAFLD, none of them perfect. Some are more suitable for studying the metabolic derangements, others for studying inflammation and fibrogenesis. The most used animals are rodents, particularly mice. NAFLD can be induced through specific diets or through genetic manipulation. This chapter will review the different animal models available, with a critical appraisal of their advantages and limitations.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

MCD:

Methionine-choline deficient

VLDL:

Very-low-density lipoprotein

SCD-1:

Stearoyl-coenzyme A desaturase-1

PEMT:

Phosphatidylethanolamine N-methyltransferase

SAMe:

S-adenosyl methionine

MAT:

Methionine adenosyltransferase

GSH:

Glutathione

ROS:

Reactive oxygen species

MTHFR:

Methylenetetrahydrofolate reductase

ALT:

Alanine aminotransferase

TGF:

Transforming growth factor

LPS:

Lipopolysaccharide

HFD:

High-fat diet

GTG:

Gold thioglucose

oxLDL:

Oxidized low-density lipoprotein

ALIOS:

American lifestyle-induced obesity syndrome

CLA:

Conjugated linoleic acid

CDAA:

Choline-deficient l-amino acids defined

DEN:

Diethylnitrosamine

JAK:

Janus kinase

STAT:

Signal transducer and activator of transcription

MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphoinositide 3-kinase

AMPK:

AMP-activated protein kinase

MC-R:

Melanocortin receptor

NOD:

Nonobese diabetic

OLETF:

Otsuka Long-Evans Tokushima fatty

CCK:

Cholecystokinin

SREBP:

Sterol regulatory element-binding protein

PEPCK:

Phosphoenolpyruvate carboxykinase

AOX:

Acyl-coenzyme A oxidase

PPAR:

Peroxisome proliferator-activated receptor

MTP:

Microsomal trifunctional protein

PTEN:

Phosphate and tensin homologue deleted on chromosome 10

KO:

Knockout

CBS:

Cystathionine β-synthase

IL:

Interleukin

IKK:

IkB kinase

NFkB:

Nuclear factor kappa β

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Duke University Medical Center, 905 LaSalle Street, Snyderman Building, Suite 1073, Durham, NC, 27710, USA

    Mariana Luisa Verdelho Moutinho Machado & Anna Mae Diehl

  2. Gastroenterology Department, Hospital de Santa Maria, CHLN, Lisbon, Portugal

    Mariana Luisa Verdelho Moutinho Machado

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  1. Mariana Luisa Verdelho Moutinho Machado
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  1. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Naga Chalasani

  2. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Gyongyi Szabo

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Machado, M.L.V.M., Diehl, A.M. (2016). Animal Models of Nonalcoholic Fatty Liver Disease. In: Chalasani, N., Szabo, G. (eds) Alcoholic and Non-Alcoholic Fatty Liver Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-20538-0_6

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