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Digestive Diseases and Sciences

, Volume 61, Issue 5, pp 1325–1336 | Cite as

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

  • Samar H. Ibrahim
  • Petra Hirsova
  • Harmeet Malhi
  • Gregory J. GoresEmail author
Review

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.

Keywords

Animal model Fibrosis Hepatocellular ballooning Inflammation Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Steatosis 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Samar H. Ibrahim
    • 1
  • Petra Hirsova
    • 2
  • Harmeet Malhi
    • 2
  • Gregory J. Gores
    • 2
    Email author
  1. 1.Division of Pediatric GastroenterologyMayo ClinicRochesterUSA
  2. 2.Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA

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