[PDF] Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame | Semantic Scholar (2024)

The most commonly used dietary, genetic, and chemical rodent models for NAFLD referring to their advantages and disadvantages are reviewed to provide critical guidance for researchers to select appropriate animal models.

A brief overview of animal models of nonalcoholic fatty liver disease with a particular focus on the basic mechanisms and physical, biochemical and histological phenotype is presented.

This article reviews the current research progress of animal models of diet-related NAFLD, and discusses the importance of establishing new dietrelatedNAFLD models, which should focus on finding pathogenic animal models that are more consistent with human dietary patterns, which is important for further understanding of NA FLD disease.

This review summarised recent histopathology and pathogenesis of NASH in humans, including the concept of resolution of inflammation, and identified the usefulness and limitations of mouse models widely used in research on NASH.

Because murine models are increasingly used to explore pharmacologic therapies for NASH, a minimum set of requirements is proposed that investigators, drug companies, and journals should consider to optimize their translational value.

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to both elucidate the pathogenesis of the disease and also to assess therapeutic interventions, and it is crucial that this aspect of the histopathology is prominent in the mouse model.

The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare and the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells.

Understanding key signaling pathways of liver inflammation in NASH is important to determine essential components that predispose, progress, or exacerbate NASH.

Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise, and so curing it is still a challenge.

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This Review discusses the prevalent dietary and inflammation-based genetic animal models described in recent years that have been undertaken using animals to model human steatosis and NAFLD to NASH disease progression.

The rearrangement of the intermediate filament cytoskeleton can be demonstrated by the loss of keratin 8/18 immunostaining of the cytoplasm, and may be evaluated in the future as a marker for the more objective detection of hepatocellular ballooning in NASH.

Patients with NAFLD require a multidisciplinary evaluation, with a major focus on type 2 diabetes mellitus and cardiovascular disease complications and may benefit from more intensive surveillance and early treatment interventions to decrease the risk for cardiovascular and kidney complications.

This rat model reproduces the key features of human NASH and provides a realistic experimental model for elucidating its treatment.

In conclusion, forced overfeeding with a high‐fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction.

It is found that long‐term high‐fat diet (HFD) exposure induces NASH, with excess body weight, hyperinsulinemia and hypercholesteremia in mice, and the murine NASH model apparently mimics clinical aspects of the condition and provides insight into NASH.

Nonalcoholic fatty liver disease is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients.

Data do not support a direct role for leptin in the pathogenesis of human NASH, and the serum leptin levels and the hepatic leptin receptor mRNA expression were not statistically different between patients with NASH and those with simple steatosis.

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