Table 2.
Current mouse models of non-alcoholic fatty liver disease
| Model | Description | DM/IR | Obese | Leptin | Fibrosis |
|---|---|---|---|---|---|
| Genetic: increased lipid import/synthesis | |||||
| ob/ob mouse | Leptin deficient. Steatosis may progress to NASH after ‘second hit’. | Y | Y | ↓ | N |
| db/db mouse | Leptin receptor deficient. Steatosis may progress to NASH after ‘second hit’. | Y | Y | ↑ | ?* |
| Yellow-obese agouti (Ay) mouse | Hyperphagic: no hypothalamic appetite suppression by melanocortin. | Y | Y | – | N |
| CD36–/– mouse | Reduced peripheral lipid uptake increases fatty acid delivery to liver. Steatosis. | N | N | – | N |
| PEPCK-NSREBP-1a mouse | Lipoatrophic model. Hepatic SREBP-1a overexpression. Develops steatosis. | Y | N | ↓ | N |
| aP2-NSREBP-1c mouse | Lipoatrophic model. SREBP-1c overexpression in adipose tissue. Steatosis. | Y | N | ↓ | N |
| aP2-Diptheria toxin mouse | Lipoatrophic model. Transgenic expression of diptheria toxin in WAT. | Y | N | ↓ | N |
| Genetic: reduced lipid export/catabolism | |||||
| PPARα–/– mouse | Impaired mitochondrial β-oxidation. Develops steatosis. | N | N | – | N |
| Acetyl CoA oxidase–/– mouse | Defective β-oxidation leads to transient steatosis. | N | N | – | N |
| Aromatase (Cyp 19)-deficient mouse | Female mice lack oestrogen. Develops steatosis. | N | Y | – | N |
| MTP–/– | Key enzyme for mitochondrial β-oxidation deleted. Develops steatohepatitis. | Y | ? | ? | ? |
| Juvenile visceral steatosis mouse | Carnitine deficiency ↓ fatty acid transport into mitochondria for β-oxidation. | N | N | – | N |
| Environmental: increased lipid import/synthesis | |||||
| High fat diet | Increased adiposity, fatty acid and insulin resistance. Steatosis and NASH. | Y | Y | ↑ | ? |
| High sucrose/fructose diet | Hepatic enzyme induction and increased fatty acid synthesis. Steatosis. | Y | Y | ↑ | ? |
| Argenine deficient | Increased lipid synthesis. Steatosis due to abnormal orotic acid metabolism. | N | N | – | N |
| Environmental: reduced lipid export/catabolism | |||||
| Methionine/choline-deficient diet | Impaired mitochondrial β-oxidation. Develops steatosis, NASH and fibrosis. | N | N | – | Y |
| Steroids, oestrogen, tamoxifen | Impaired mitochondrial β-oxidation and reduced hepatic triglyceride secretion. | Y | Y | – | – |
*
Fibrosis may be reduced in the db/db mouse model.