An Overview of Mouse Models of Nonalcoholic Steatohepatitis: From Past to Present

Jacobs, Ans; Warda, Anne-Sophie; Verbeek, Jef; Cassiman, David; Spincemaille, Pascal

doi:10.1002/cpmo.3

Cited by 43 publications

(39 citation statements)

References 115 publications

(150 reference statements)

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“…In the late 1990s, it was shown that a diet deficient in methionine and choline (MCD) caused severe steatohepatitis in rodents, albeit with wasting . Since then, numerous other models with diverse pathogenic mechanisms, metabolic features, histopathology, and disease progression have been evaluated, as summarized in several reviews . In the face of such diversity and the pressing need for “optimal” NASH models for preclinical drug development, it is timely to reflect on appropriate criteria for animal models to mimic human NASH.…”

Section: Animal Models Of Nafld and Nashmentioning

confidence: 99%

“…These are summarized in Table , and original references are cited in several reviews . Overnutrition can be obtained by use of HFDs, but in most strains of mice body weights exceeding 40 g (obese for mice) are not achieved.…”

Section: Types Of Nash Modelsmentioning

confidence: 99%

“…Genetic models of NASH are summarized in Table and described in detail in several reviews . Voluntary overeating occurs in mice with single mutations of appetite‐regulating genes, especially ob/ob (leptin‐deficient), db/db (deficient leptin signaling), foz/foz (spontaneous mutations in the Alström syndrome 1 gene, which encodes a protein localized to centrosomes and appetite‐sensing neuronal cilia), and melanocortin receptor 4 knockout ( Mc4r –/– ) mice resembling obesity in humans.…”

Section: Types Of Nash Modelsmentioning

confidence: 99%

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Mouse Models of Nonalcoholic Steatohepatitis

et al. 2019

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Nonalcoholic steatohepatitis (NASH) arises from a variable interplay between environmental factors and geneticdeterminants that cannot be completely replicated in animals. Notwithstanding, preclinical models are needed to understand NASH pathophysiology and test mechanism-based therapies. Among several mouse models of NASH, some exhibit the key pathophysiologic as well as histopathologic criteria for human NASH, whereas others may be useful to address specific questions. Models based on overnutrition with adipose restriction/inflammation and metabolic complications, particularly insulin resistance, may be most useful to investigate critical etiopathogenic factors. In-depth pathologic description is required for all models. Some models demonstrate hepatocyte ballooning, which can be confused with microvesicular steatosis, whereas demonstration of an inflammatory infiltrate and pattern of liver fibrosis compatible with human NASH is desirable in models used for pharmacologic testing. When mice with specific genetic strains or mutations that cause overeating consume a diet enriched with fat, modest amounts of cholesterol, and/ or simple sugars ("Western diet"), they readily develop obesity with liver disease similar to human NASH, including significant fibrosis. Purely dietary models, such as high-fat/high-cholesterol, Western diet, and choline-deficient, amino acid-defined, are similarly promising. We share concern about using models without weight gain, adipose pathology, or insulin resistance/hyperinsulinemia and with inadequate documentation of liver pathology. NASH-related fibrosis is a key endpoint in trials of possible therapies. When studied for this purpose, NASH models should be reproducible and show steatohepatitis (ideally with ballooning) and at least focal bridging fibrosis, while metabolic factors/disordered lipid partitioning should contribute to etiopathogenesis. Because murine models are increasingly used to explore pharmacologic therapies for NASH, we propose a minimum set of requirements that investigators, drug companies, and journals should consider to optimize their translational value. (Hepatology 2019;69:2241-2257).

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Section: Animal Models Of Nafld and Nashmentioning

confidence: 99%

Section: Types Of Nash Modelsmentioning

confidence: 99%

Section: Types Of Nash Modelsmentioning

confidence: 99%

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Mouse Models of Nonalcoholic Steatohepatitis

et al. 2019

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“…High-fat diet (HFD) is widely used to building NAFLD animal models. This group of diets consists of a variety of regimens with fat content varying between 45 and 75 kcal% [16]. Lieber et al [17] reported a rat model using HFD (71% of calories from fat, 11% from carbohydrates, and 18% from proteins).…”

Section: High-fat Dietmentioning

confidence: 99%

Rodent Models of Nonalcoholic Fatty Liver Disease

Zhong

Zhou²,

et al. 2019

Digestion

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Background: Nonalcoholic fatty liver disease (NAFLD) is a continuous diseases spectrum associated with obesity, type 2 diabetes, insulin resistance, and hyperlipidemia. Simple hepatic steatosis may progress to nonalcoholic steatohepatitis (NASH), even fibrosis and cirrhosis, and finally hepatocellular carcinoma. In recent years, NAFLD has become a public health concern with increasing prevalence. However, the mechanisms underlying the pathogenesis remain incompletely understood, and few effective therapeutic approaches are available. Summary and Key Messages: A myriad of different rodent models has been developed to elucidate pathophysiology of NAFLD/NASH and guide therapeutic strategy. To date, no single rodent model can display the whole disease spectrum and metabolic features associated with human NASH, but can imitate particular characteristics. In this paper, we review the most commonly used dietary, genetic, and chemical rodent models for NAFLD referring to their advantages and disadvantages. Also, we illustrate the status of latest treatment strategy using various NAFLD rodent models. We hope to provide critical guidance for researchers to select appropriate animal models.

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“…One of the simplest ways of disturbing lipid metabolism, inducing steatosis and moderate NASH, is by the administration of a regular high-fat diet (HFD; 60% fat, 20% proteins, 20% carbohydrates) [18,19]. For instance, feeding wild-type C57BL/6 mice a HFD for 10-12 weeks resulted in phenotypic changes such as hyperlipidemia, hyperinsulinemia, and glucose intolerance [19,20].…”

Section: Dietary Murine Modelsmentioning

confidence: 99%

NAFLD Preclinical Models: More than a Handful, Less of a Concern?

Oligschlaeger

Shiri-Sverdlov

2020

Biomedicines

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and/or hepatocellular carcinoma. Due to its increasing prevalence, NAFLD is currently a major public health concern. Although a wide variety of preclinical models have contributed to better understanding the pathophysiology of NAFLD, it is not always obvious which model is best suitable for addressing a specific research question. This review provides insights into currently existing models, mainly focusing on murine models, which is of great importance to aid in the identification of novel therapeutic options for human NAFLD.

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An Overview of Mouse Models of Nonalcoholic Steatohepatitis: From Past to Present

Cited by 43 publications

References 115 publications

Mouse Models of Nonalcoholic Steatohepatitis

Mouse Models of Nonalcoholic Steatohepatitis

Rodent Models of Nonalcoholic Fatty Liver Disease

NAFLD Preclinical Models: More than a Handful, Less of a Concern?

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