Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a disease of increasing interest as its prevalence is on the rise. NAFLD has been linked to metabolic syndrome, which is becoming more common due to the Western diet. Since NAFLD can lead to cirrhosis and related complications including hepatocellular carcinoma, the increasing prevalence is concerning and medical therapy aimed at treating NAFLD is of great interest. Researchers studying the effects of medical therapy on NAFLD use dietary mouse models. The two main types of mouse model diets are the methionine- and choline-deficient (MCD) diet and Western-like Diet (WD). Although both induce NAFLD, the mechanisms are very different. We reviewed several studies conducted within the last 5 years that use MCD diet or WD mouse models in order to mimic this disease in a way most similar to humans. The MCD diet inconsistently induces NAFLD and fibrosis and doesn’t completely induce metabolic syndrome. Thus, the clinical significance of the MCD diet is questionable. In contrast, WD mouse models consisting of high fat, cholesterol, and a combination of high fructose corn syrup, sucrose, fructose or glucose not only lead to metabolic syndrome but also induce NAFLD with fibrosis making these choices most suitable for research.

Optimization of In vivo Imaging Provides a First Look at Mouse Model of Non-Alcoholic Fatty Liver Disease (NAFLD) Using Intravital Microscopy

“…It is thought this rather "acute" model of liver disease does not accurately recapitulate the chronic tissue remodeling that occurs over a period of decades in humans. Considering this, we have implemented a 20 week high fat diet (HFD) for mice that better models the clinical course of NAFLD development (7).…”

Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of non-alcoholic steatohepatitis

“…Likewise, Western-type diets of varying composition with respect to fat (21-45 kcal%), cholesterol (0.1-2%), and sugars (e.g., 20% fructose) closely mimic the pathogenesis of human NASH, i.e., insulin resistance, inflammation and liver fibrosis; regardless of the composition, however, the NASH phenotype manifested only after a relatively long-term diet duration of 8 to 30 weeks [2,9]. C57BL/6J mice fed a methionine-and choline-deficient diet develop a NASH phenotype in the shortest time compared with all previous NASH models, with hepatic steatosis by 2-4 weeks and progression to inflammation and fibrosis shortly thereafter, although animals lose weight and do not develop insulin resistance [25,26].…”

“…Indeed, an appropriate animal model should recreate as closely as possible the pathological patterns, metabolic and transcriptomic features, and histological alterations found in human NASH. Several preclinical mouse and rat models for NASH are currently available, with various approaches based on genetic modification, e.g., ob -/obor db -/dbmice with leptin and leptin receptor deficiency, respectively, diet induction, e.g., high-fat/cholesterol/fructose diet or methionine/cholinedeficient diet, or chemical induction, e.g., thioacetamide or carbon tetrachloride [2,8,9]. Each of these models can be used separately or in combination.…”

Autocrine IL11 cis-signaling in hepatocytes is an initiating nexus between lipotoxicity and non-alcoholic steatohepatitis

“…In addition to rapidly stimulating lipotoxicity-driven NASH [31] the HFMCD diet causes weight loss [31]. Surprisingly, weight loss in mice on the HFMCD diet was initially limited and later reversed in CKO mice (Fig.…”