Modeling Diet-Induced NAFLD and NASH in Rats: A Comprehensive Review

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, characterized by hepatic steatosis without any alcohol abuse. As the prevalence of NAFLD is rapidly increasing worldwide, important research activity is being dedicated to deciphering the underlying molecular mechanisms in order to define new therapeutic targets. To investigate these pathways and validate preclinical study, reliable, simple and reproducible tools are needed. For that purpose, animal models, more precisely, diet-induced NAFLD and nonalcoholic steatohepatitis (NASH) models, were developed to mimic the human disease. In this review, we focus on rat models, especially in the current investigation of the establishment of the dietary model of NAFLD and NASH in this species, compiling the different dietary compositions and their impact on histological outcomes and metabolic injuries, as well as external factors influencing the course of liver pathogenesis.

Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements

“…Our experimental animals were obese, with a bland NAFLD and metabolic impairment indicative of an early stage of the disease. To further investigate the effects of the treatments used on more advanced forms of fatty liver disease, further research on more advanced NASH animal models is warranted; combined HF + high sugar diets over an extended time frame seem to induce more inflammatory and fibrotic changes [66]. For these reasons, the present study is less meaningful concerning the more advanced inflammatory form of fatty liver disease.…”

“…Using both methods would have allowed a more accurate statement regarding the insulin resistance of the animals. Moreover, the animal model of HFD-induced obesity in rats contains distinct advantages and disadvantages: on the one hand, rats on HFD develop marked obesity within a short period of time and show greater biochemical similarities with humans, especially compared to mice [65,66]. Furthermore, compared to diets with modified amino acids or genetic models of adiposity, HFD-models mimic the Western diet, which is seen as one of the most relevant drivers of the obesity pandemic [67][68][69].…”

“…Furthermore, compared to diets with modified amino acids or genetic models of adiposity, HFD-models mimic the Western diet, which is seen as one of the most relevant drivers of the obesity pandemic [67][68][69]. On the other hand, animals under HFD usually do not show advanced fatty liver disease states such as with severe inflammation or marked fibrotic changes of the liver, as found in human alimentary NAFLD/NASH, even after longer feeding periods, although inflammatory aspects of progressive NAFLD can be detected [66]. Our experimental animals were obese, with a bland NAFLD and metabolic impairment indicative of an early stage of the disease.…”

Pathogenesis from Inflammation to Cancer in NASH-Derived HCC

“…While a large number of models of NASH have been described, such as methionine and choline deficient diet model, choline-deficient L-amino-defined diet model, fructose and cholesterol diet model, high fat high sugar diet model, leptin deficiency (ob/ob mice) model, and leptin receptor deficiency (db/db mice) model. [112][113][114] These models have several limitations, including the necessity of non-physiological dietary manipulations, or the lack of insulin resistance or liver histology characteristic of NASH in humans, and rarely developed advanced fibrosis and do not lead to HCC. [112][113][114] Recently, an isogenic B6/129 hybrid strain of genetically modified mice was fed a western diet with a high-fructose-sugar solution and described as a new animal NASH-derived HCC model that faithfully recapitulates the progression of the human disease, and is expected to become a pre-clinical model in the transition from inflammation to cancer in NASH research.…”

Investigating the antioxidant effects of Aloe vera: Possible role in regulating lipid profile and liver function in high fat and fructose diet (HFFD) fed mice

“…A strong correlation between obesity and hyperglycemia has been reported in previous studies and it often results in fatty liver disease [3]. Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis and about five per increase in triglycerides with no evidence of alcohol abuse [4]. Obesity and diabetes are the most common risk factors of NAFLD.…”