Table 1.
Murine and non-murine models of NAFLD/NASH with or without atherosclerosis
| Disease Model | Animal Model | Diet Source | Diet Components | Time on Diet | Phenotype | References |
|---|---|---|---|---|---|---|
| Murine models | ||||||
| NAFLD | Mouse (C57BL/6J) Apoe-/- |
Mucedola, Milan, Italy | Western-type Diet: 21.2% kCal from fat 0.2% cholesterol |
24 weeks | Normal hepatic histology with no triglyceride accumulation noted | Karavia et al. (99) |
| NAFLD | Mouse (C57BL/6J) | Envigo | Fructose-palmitate diet (TD.160785): 190g/kg hydrogenated vegetable shortening 40g/kg anhydrous milk fat 0.2%–0.5% cholesterol 55% glucose/45% fructose w/w in the drinking water |
16 weeks | Enhanced steatosis but no fibrosis | Wang et al. (76) |
| NASH | Mouse (C57BL/6J) Apoe-/- |
No information provided | High-fat diet No additional information provided |
8 weeks | Enhanced plasma AST/ALT, hepatic steatohepatitis, ballooning, and fibrosis | Lu et al. (100) |
| NASH | Mouse (C57BL/6J) | Oriental Yeast, Tokyo, Japan | Atherogenic diet: 14g fat 1.25% cholesterol High fat diet 60g fat 1.25% cholesterol |
12–24 weeks | Enhanced steatosis, inflammation, and fibrosis observed in atherogenic and high fat diet combined, but not atherogenic diet alone | Matsuzawa et al. (101) |
| NASH | Mouse (C57BL/6J) | Research Diets, New Brunswick, NJ Envigo |
High-fat diet (D12492): 60% fat 0.03% cholesterol Choline-deficient high fat diet (D05010402) 60% fat 0.03% cholesterol Choline deficient Western diet (TD.88137): 42% fat, 0.2% cholesterol |
15 weeks | Enhanced steatosis. Inflammation only observed in Western diet. Fibrosis only observed in choline deficient high fat diet and Western diet. | Smati et al. (124) |
| NASH | Mouse (C57BL/6J) | Teklad | Fructose-palmitate-cholesterol (TD.140154): 190g/kg hydrogenated vegetable shortening 40g/kg anhydrous milk fat 1.25% cholesterol ~35% reduction in choline 55% glucose/45% fructose w/w in the drinking water |
8–28 weeks | Enhanced steatohepatitis and fibrosis | Wang et al. (74) |
| NASH | Mouse (C57BL/6J) | Envigo | Fructose-palmitate diet (TD.160785): 190g/kg hydrogenated vegetable shortening 40g/kg anhydrous milk fat 1.25% cholesterol ~35% reduction in choline 55% glucose/45% fructose w/w in the drinking water |
16 weeks | Enhanced steatohepatitis and fibrosis | Wang et al. (76) |
| NASH | Mouse (Lepob/Lepob) |
Research Diets, New Brunswick, NJ | High trans-fat, high fructose, high cholesterol diet (HTF): 40% kCal fat from vegetable shortening 22% w/w fructose 2% cholesterol |
12 weeks for trans-fat diet | Enhanced hepatic steatosis and fibrosis | Trevaskis et al. (104) |
| NASH | Mouse (C57BL/6J) | Research Diets, New Brunswick, NJ | NASH diet (D17010103): 40% kCal fat with 50g/kg primex shortening (non-transfat), 122g/kg corn oil, partially hydrogenated 22% w/w fructose 2% cholesterol |
24 weeks | Enhanced AST, ALT, and ALP, with enhanced steatohepatitis and fibrosis | Rom et al. (96, 97) |
| NASH-HCC | Mouse (C57BL/6J) | Specialty Feeds, Glenn Forrest, WA | High-fat/high-cholesterol diet: 43.7% fat 0.203% cholesterol |
8–14 months | Enhanced AST, ALT, steatohepatitis, and fibrosis beginning at 8 months, and HCC observed by 10 months | Zhang et al. (102) |
| NASH and Atherosclerosis | Mouse (C56BL/6J) Ldlr-/-.Leiden |
Research Diets, New Brunswick, NJ | High-fat diet (D12451): 45% kCal fat from lard 35% kCal carbohydrates from sucrose 0.01% w/w cholesterol Fast food diet: 41% kCal fat from milk fat 44% kcal carbohydrates from fructose 0.05% w/w cholesterol |
28 weeks | Enhanced AST, ALT, hepatic steatohepatitis, fibrosis, and atherosclerosis | Van den Hoek et al. (86) |
| Non-murine models | ||||||
| Coronary artery disease | Ossabaw pig | No information provided | Western diet: 38% kCal fat 1.5% cholesterol w/w |
6 months | Significant increases in ALP, ALT, AST (but no liver histology noted), and coronary artery lesions compared with control diet | Matthan et al. (133) |
| NASH | Ossabaw pig | Purina TestDiet, Inc., Richmond, IN | Atherogenic diet: 46% kCal fat 20% kCal fructose 2% cholesterol 900 ppm choline Modified atherogenic diet: 43% kCal fat 17.8% fructose 2% cholesterol 700ppm choline |
24 weeks | Enhanced AST and ALT, steatohepatitis, ballooning, and fibrosis in modified atherogenic diet group. Enhanced ALT and steatosis in atherogenic diet group. | Lee et al. (134) |
| NASH with fibrosis by NaNO2 injections | Wistar rat | Research Diets, New Brunswick, NJ | Choline deficient high fat diet (A06071302): 60% kcal fat 0.03% cholesterol 0.1% methionine Choline deficient NaNO2 injections: 10-30mg/kg |
10 weeks, with NaNO2 administered following 4 weeks | Enhanced fibrosis | Schwabl et al. (126) |
| NASH and atherosclerosis | Japanese white rabbit | No information provided | High-fat and -cholesterol diet: 12% corn oil 0.75% cholesterol |
9 months | Enhanced steatohepatitis, hepatic fibrosis, and aortic atheroma | Ogawa et al. (135) |
| NASH and atherosclerosis by aortic endothelial injury by balloon catheter | Rabbit | TestDiet, Saint Louis, MO | Cholesterol containing chow diet: 2.4% fat w/w 1% cholesterol |
3 months | Enhanced hepatocyte ballooning and fibrosis. Atherosclerosis only enhanced with cholesterol diet and injury | Taylor et al. (139) |
| NASH | Cynomologus monkey | Kunming Biomed International | High fat diet: 20% fat, 5% cholesterol |
3 years | Enhanced steatohepatitis, fibrosis, and NAS score | Lyu et al. (142) |
| NASH | Cynomologus monkey | Beijing Keao Xieli Feed Co., Ltd, Beijing, China | High fat high cholesterol diet: 10% lard 15% cholesterol |
24 weeks | Enhanced steatohepatitis, hepatic ballooning, fibrosis, and NAS score | Jian et al. (143) |
| NASH | Cynomologus monkey | Keao Xieli | High fat high cholesterol diet: 10% lard 1% cholesterol |
16 weeks | Enhanced NAS score, steatosis, and fibrosis | Zang et al. (144) |