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Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame

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Abstract

With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health problem with increasing prevalence. The mechanism of disease progression remains obscure and effective therapy is lacking. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary, especially, since causative mechanistic studies of NAFLD are more difficult or unethical to perform in humans. A large number of studies regarding the pathophysiology and treatment of nonalcoholic steatohepatitis (NASH) have been undertaken in mice to model human NAFLD and NASH. This review discusses the known dietary, genetic, and inflammation-based animal models of NASH described in recent years, with a focus on the major advances made in this field.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

MCD:

Methionine and choline deficient

CDAA:

Choline-deficient l-amino-defined

VLDL:

Very low-density lipoprotein

HFD:

High-fat diet

FF:

Fast food

HF:

High fat

FFC:

High fat, fructose, and cholesterol

HF-HSD:

High-fat high-sugar diet

SREBP-1:

Sterol regulatory element-binding protein 1

PTEN:

Phosphatase and tensin homolog

PPARα:

Peroxisome proliferator-activated receptor α

AOX:

Acyl-coenzyme A oxidase

MAT1A:

Methionine adenosyl transferase

MCP-1:

Monocyte chemotactic protein 1

CCR-2:

Chemokine (C–C motif) receptor 2

TLR:

Toll-like receptor

My88:

Myeloid cell differentiation 88

MD-2:

Myeloid differentiation protein 2

JNK:

C-jun N-terminal kinase

MLK:

Mixed lineage kinase 3

IL:

Interleukin

NLR:

NOD-like receptors

NLRP3:

NOD-, LRR-, and pyrin domain-containing 3

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Acknowledgments

The authors thank Courtney Hoover for her excellent secretarial assistance, Dr. Thomas Smyrk, and Dr. Kyoko Tomita for their help in acquiring the histological pictures.

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Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Mayo Clinic, Rochester, MN, USA

    Samar H. Ibrahim

  2. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Petra Hirsova, Harmeet Malhi & Gregory J. Gores

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  1. Samar H. Ibrahim
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Correspondence to Gregory J. Gores.

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Ibrahim, S.H., Hirsova, P., Malhi, H. et al. Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame. Dig Dis Sci 61, 1325–1336 (2016). https://doi.org/10.1007/s10620-015-3977-1

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