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

Abstract

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.

Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments

“…Although the STAM model gives rise to liver steatosis, inflammation and fibrosis, these animals develop conditions that resemble type 1 rather than type 2 diabetes, as indicated by the overt hyperglycaemia (blood glucose 600 mg/dl) and a lack of hyperinsulinemia, a sign of insulin resistance (plasma insulin <0.5 ng/ml) ( Saito et al, 2017 ). Although the STAM model has been discussed in other reviews, consideration of the combination of STZ and HFD (STZ + HFD) where STZ was delivered at a later stage of the animal’s life is less frequently noted ( Friedman et al, 2018a ; Farrell et al, 2019 ; Oligschlaeger and Shiri-Sverdlov, 2020 ). FVB/N mice which received STZ (55 mg/kg) at 6 weeks old coupled to a HFD displayed hyperinsulinemia ( Tate et al, 2019 ).…”

A human pluripotent stem cell model for the analysis of metabolic dysfunction in hepatic steatosis

“…For example, although the leptin-deficient Ob/Ob mouse develops extreme obesity and metabolic abnormalities, the profound abnormalities in circulating leptin mean that this model is not representative of human disease in the general population ( Anstee and Goldin, 2006 ; Rotundo et al., 2018 ). Likewise, dietary interventions mimic specific stages of NAFLD, such as steatosis or inflammation, but do not reflect the disease progression that occurs in humans ( Oligschlaeger and Shiri-Sverdlov, 2020 ). A common dietary intervention is the methyl-donor-deficient (MDD) diet, which recapitulates the inflammatory responses associated with NASH but not the other elements of the metabolic syndrome ( Lyall et al., 2017 ; Rinella and Green, 2004 ).…”

Emerging Role of Nuclear Receptors for the Treatment of NAFLD and NASH

“…Non-alcoholic fatty liver (NAFLD) is the most prevalent chronic liver disease worldwide. NAFLD comprises a spectrum of diseases from simple steatosis (greater than 5% hepatic fat) to steatohepatitis (combination of lipid accumulation and inflammation and/or fibrosis) ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 ]. In some cases, this disease can progress into advanced-stage liver diseases including cirrhosis or hepatocellular carcinoma (HCC).…”