Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

Blueberry (<i>Vaccinium virgatum</i> Aiton) Leaf Infusion Ameliorates Insulin Resistance in Mice Fed a High-fat, High-sucrose Diet

“…For instance, chlorogenic acid and rutin ameliorate HFHSD-induced lipid and glucose metabolism (Takahashi et al 2014, Panchal et al 2011, 2012. Moreover, proanthocyanidin should be considered an active component because grape seed extract-derived proanthocyanidins showed potent antioxidant activity and prevented high-fructose diet-induced insulin resistance (Suwannaphet et al 2010).…”

Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

“…Not only does the baseline liver biopsy reduce biological variability by excluding mice that fail to develop NASH prior to initiating therapy, but it also allows for within-subject comparisons over time, thereby increasing statistical power [6] . For the genetically modified NASH models, several studies have implicated a role of individual genes involved in the development of NASH using deletion or overexpression models [7,9] . For example, mice that overexpress the transcription factor sterol regulatory element-binding proteins (SREBPs), a feedback regulatory system controlling intracellular levels of cholesterol and free fatty acids develop a hepatic phenotype resembling NASH.…”

“…Other dietary models involve feeding nutrient-deficient diets such as the methionineand choline-deficient diet (MCD). Methionine and choline deficiency impairs liver β-oxidation and the production of very-low density lipoproteins (VLDL) hereby generating a "second hit" [1] , eliciting a more severe fibrotic NASH phenotype within hepatic tissue [8,9] .…”

Cholesterol Metabolism and Its Regulation by Functional Foods

“…SREBP-1c overexpression in the liver of transgenic mice produces a rich in triglycerides fatty liver without increasing cholesterol, whereas SREBP-2 over expression in transgenic mice results in a 28% increment in cholesterol synthesis. In rat hepatocytes, insulin treatments increase the total amount of SREBP-1c 14 .…”

“…Hu y col, found that a 1% cholesterol diet in rats show a decrease of more than 50% of the serum triglyceride levels, but increases the hepatic levels of them, also the serum and liver figures of the molecule are maintained 13 . Other studies made, in laboratory animals, have tried also to establish the metabolic behavior of these diets: rats fed high cholesterol diets have an increment in serum and hepatic cholesterol concentration 14 . Rats show an increment in serum and hepatic triglyceride levels, which conditions a non-alcoholic liver disease (NAFLD).Given this evidence, it can be established a relationship between dietary cholesterol and triglyceride metabolism, which is evident mainly in the liver tissue.…”