Table 1. . Animals models in NAFLD and hepatocellular carcinoma development.
Obesity | Insulin resistance | Inflammation | NASH | Fibrosis | HCC | |
---|---|---|---|---|---|---|
Diet models | ||||||
MCD Deficient in choline and methionine 10% fat, 40% sucrose, |
- (weight loss) |
- | + |
++ (3 weeks) |
++ (5–8 weeks) |
- |
CDAA Deficient in choline, defined L-amino acid |
+ | + | + | + | + | - |
HFD >60% fat, no increase in sugar or cholesterol |
++ | ++ | + | ± (strain dependent) |
- | - |
WD >40% fat, 0.2–1% cholesterol, high sucrose |
++ | - | + | ± (strain dependent) |
± (strain dependent) |
- |
High cholesterol-high fructose >40% fat, 0.2% cholesterol, high fructose |
++ | ++ | ++ | ++ | ++ | ++ |
CDAA-HFD Deficient in choline, defined L-amino acid >60% fat, 0.2% cholesterol |
++ | ++ | ++ |
++ (8–12 weeks) |
+ (16–24 weeks) |
+ (24–36 weeks) |
Toxins/diet-based models | ||||||
STAM model STZ + HFD |
- | ++ | ++ | ++ | + |
++ (16–20 weeks) |
HFD + DEN | ++ | ++ | ++ | - | - |
++ (20 weeks) |
CDAA-HFD + DEN | ++ | ++ | ++ | - | - |
++ (20 weeks) |
WD + CCl4 | + | + | ++ | + | + |
++ (24 weeks) |
Genetic/toxic/diet-based models | ||||||
PTEN-/-(PMID 15199412) Deletion of PTEN, a tumor-suppressor gene No specific diet |
- | ++ | ++ | ++ | ++ |
+ (44 weeks) |
AOX-/- Deletion of acyl-coenzme A Inhibition of β-oxydation No specific diet |
- | - | ++ | + | + |
+ (60 weeks) |
MAT1A-/- Deletion of methionine adenosyltransferase No specific diet |
- | - | ++ |
+ (32 weeks) |
- |
+ (72 weeks) |
foz/foz Alms1 mutation, cilial disorder affecting appetite regulation Fed with 40% fat, 0.2% cholesterol, 34% sucrose |
++ | ++ | ++ |
++ (16 weeks) |
++ (moderate fibrosis at 24–36 weeks) |
++ (52 weeks) |
foz/foz Alms1 mutation, cilial disorder affecting appetite regulation Injected with DEN |
++ | ++ | ++ | + | + |
++ (24 weeks) |
PPARα-/- PPAR-γ causes insulin sensitization and enhances glucose metabolism Injected with DEN |
++ | - | ++ | ++ | ++ |
+ (24 weeks) |
Liver-specific Hnf4α-deficient mice Hnf4α regulates genes involved in lipid and bile acid synthesis, gluconeogenesis, amino acid metabolism and blood coagulation Fed with HFD |
++ | - | + | + | + |
+ (36 weeks |
Mc4r-/- mice Mutation of appetite regulation gene Fed with 40% fat, 0.2% cholesterol, 34% sucrose |
++ | ++ | + |
++ (20 weeks) |
++ (20 weeks) |
+ (48 weeks) |
MUP-uPA Tg Express high amounts of uPA Fed with HFD |
++ | ++ | ++ |
++ (16 weeks) |
++ |
++ (40 weeks) |
DIAMOND Inbred isogenic strain: 60% C57Bl6/J, 40% S129S1/svlm Fed with 42% fat, 0.1% cholesterol, ad libitum glucose/fructose in drinking water |
++ | ++ | ++ |
++ (16 weeks) |
++ (advanced fibrosis at 36 weeks) |
++ (52 weeks) |
ALMS1: Alstrom syndrome 1 gene; AOX: Acyl-coenzyme A oxidase; CCl4: Carbon tetrachloride; CDAA: Choline-deficient L-amino acid-defined; DEN: Diethylnitrosamine; DIAMOND: Diet-induced animal model of NAFLD; HCC: Hepatocellular carcinoma; HFD: High fat diet; MAT1A: Methionine adenosyltransferase 1A; MCD: Methionine choline deficient; MC4R: Melanocortin receptor 4 knockout; NASH: Non-alcoholic steatohepatitis; PTEN: Phosphatase and tensin homolog; STZ: Streptozotocin; uPA: Urokinase plasminogen activator; WD: Western diet.