Dietary methods to induce NAFLD/NASH in rodents can be split into two common categories:

• diets fed for longer periods of time to induce obesity, metabolic syndrome, and mild NASH or
• diets fed for short periods of time to induce hepatic features of severe NASH without inducing obesity or insulin resistance

This page provides further information on dietary methods to induce NAFLD/NASH. We’ve also prepared a downloadable NASH/NAFLD mini paper.

The tables below highlight diet options from both of the above categories. For more complete descriptions of NAFLD/NASH models see the drop down menus that follow the tables.

在啮齿动物中诱发 NAFLD/NASH 的饮食方法可分为两个常见类别：

喂食较长时间的饮食会诱发肥胖、代谢综合征和轻度 NASH 或
短时间喂食以诱发严重 NASH 的肝脏特征而不诱发肥胖或胰岛素抵抗的饮食
本页提供了有关诱发 NAFLD/NASH 的饮食方法的更多信息。 我们还准备了可下载的 NASH/NAFLD 迷你论文。

下表突出显示了上述两个类别的饮食选择。 有关 NAFLD/NASH 模型的更完整描述，请参见表格后面的下拉菜单。

order today

18301939375

上海金畔生物科技有限公司

• Western or fast food style diets fed to induce NASH with metabolic syndrome contain 40 – 45% kcal from milkfat (a fat source high in palmitate) with added cholesterol (0.15 – 2%) and are high in sucrose (>30%). Dietary palmitate and cholesterol have both previously been associated with the progression from simple steatosis to NASH.

  导致肥胖、代谢综合征和轻度 NAFLD/NASH 的饮食
  用于诱发患有代谢综合征的 NASH 的西式或快餐式饮食含有 40 – 45% 来自乳脂（棕榈酸酯含量高的脂肪来源）的 kcal，并添加了胆固醇（0.15 – 2%），并且蔗糖含量高（>30%）。 膳食棕榈酸酯和胆固醇以前都与从简单脂肪变性到 NASH 的进展有关。

  Examples:

  • TD.88137 Adjusted Calories Diet (42% from fat)
  • TD.96121 21% MF, 1.25% Chol. Diet
  • TD.120528 42% Kcal/Fat Diet (Incr. Sucrose, 1.25% Chol.)
    

    Western and Fast Food diets with milkfat and cholesterol

  Research use:

  These diets can induce obesity, metabolic syndrome, and simple steatosis within nine weeks of feeding. Increased hepatic inflammation has been observed after 12 weeks of feeding. NASH typically requires longer feeding with fibrosis developing within nine months and late stage fibrosis including hepatic ballooning occurring after 14 – 20 months of feeding. Increasing dietary sucrose (~41%) and cholesterol (~1.25%) accelerates the NASH phenotype with steatosis, inflammation and hepatocyte ballooning observed within 12 weeks. In addition to feeding a high fat diet, providing a glucose/fructose mixture in the drinking water may further promote NASH development.

  研究用途：

  这些饮食会在喂食后的九周内诱发肥胖、代谢综合征和单纯性脂肪变性。 喂养 12 周后观察到肝脏炎症增加。 NASH 通常需要更长的喂养时间，在 9 个月内出现纤维化，在 14-20 个月的喂养后出现包括肝气球样变在内的晚期纤维化。 增加膳食蔗糖 (~41%) 和胆固醇 (~1.25%) 会加速 NASH 表型，在 12 周内观察到脂肪变性、炎症和肝细胞膨胀。 除了喂食高脂肪饮食外，在饮用水中提供葡萄糖/果糖混合物可能会进一步促进 NASH 的发展。

  Select References:  参考文献

  Charlton, M., et al., Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am J Physiol Gastrointest Liver Physiol, 2011. 301(5): p. G825-34. www.ncbi.nlm.nih.gov/pubmed/21836057

  Gores, G., Charlton M, Krishnan A, Viker K, Sanderson S, Cazanave S, McConico A, Masuoko H. Am J Physiol Gastrointest Liver Physiol, 2015. 308: p. G159. ajpgi.physiology.org/content/308/2/G159

  Li, Z.Z., et al., Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem, 2009. 284(9): p. 5637-44. www.ncbi.nlm.nih.gov/pubmed/19119140

  Ioannou, G.N., et al., Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis. J Lipid Res, 2009. 54(5): p. 1326-34. www.ncbi.nlm.nih.gov/pubmed/23417738

  Alkhouri, N., et al., Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem, 2010. 285(5): p. 3428-38. www.ncbi.nlm.nih.gov/pubmed/19940134

  Dixon, L.J., et al., Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS One, 2013. 8(2): p. e56100. www.ncbi.nlm.nih.gov/pubmed/23409132

  DeLeve, L.D., et al., Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am J Pathol, 2008. 173(4): p. 993-1001. www.ncbi.nlm.nih.gov/pubmed/18772330

  VanSaun, M.N., et al., High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model. Am J Pathol, 2009. 175(1): p. 355-64. www.ncbi.nlm.nih.gov/pubmed/19541928

  Asgharpour, A., et al., A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol, 2016. 65(3): p. 579-88. www.ncbi.nlm.nih.gov/pubmed/27261415

  Tetri, L.H., et al., Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol, 2008. 295(5): p. G987-95. www.ncbi.nlm.nih.gov/pubmed/18772365

  Tsuchida, T., et al., A simple diet-and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. Journal of hepatology, 2018. 69(2):385-395. www.ncbi.nlm.nih.gov/pubmed/29572095

• The ALIOS model: western diet with trans-fat

  The American Lifestyle-Induced Obesity Syndrome (ALIOS) model involves feeding the “American fast food” diet high in trans-fats and sugar. Dietary trans-fats from hydrogenated vegetable shortening (HVO) are associated with increased insulin resistance and hepatic inflammation in rodent NASH models. In addition to diet, a glucose/fructose solution is added to the drinking water and sedentary behavior promoted by removing the overhead cage feeders in this model.

  ALIOS 模型：含有反式脂肪的西方饮食
  美国生活方式诱发的肥胖综合症 (ALIOS) 模型涉及喂食富含反式脂肪和糖的“美国快餐”饮食。 来自氢化植物起酥油 (HVO) 的膳食反式脂肪与啮齿动物 NASH 模型中胰岛素抵抗和肝脏炎症的增加有关。 除了饮食，葡萄糖/果糖溶液被添加到饮用水中，并且通过移除该模型中的架空笼式喂食器来促进久坐行为。

  Examples:

  • TD.06303 22% HVO Diet
  • TD.120330 22% HVO + 0.2% Cholesterol Diet
  • TD.130885 ALIOS with Added Sugar

   

  Research use:

  The ALIOS model develops obesity with insulin resistance, elevated ALT levels, and steatosis within 16 weeks. Increased inflammation and early development of fibrosis have been observed at 6 months. Severe steatosis with fibrosis and inflammation develops within 12 months of feeding with 50% of the mice reportedly developing hepatic neoplasms. Adding cholesterol (0.2%) to the American Fast Food diet may accelerate NASH phenotype development.

  研究用途：

  ALIOS 模型在 16 周内发展为具有胰岛素抵抗、ALT 水平升高和脂肪变性的肥胖症。 在 6 个月时观察到炎症增加和纤维化的早期发展。 喂食后 12 个月内会出现伴有纤维化和炎症的严重脂肪变性，据报道有 50% 的小鼠会出现肝肿瘤。 在美国快餐饮食中添加胆固醇（0.2%）可能会加速 NASH 表型的发展。

  Select References: 参考文献

  Koppe, S.W., et al., Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am J Physiol Gastrointest Liver Physiol, 2009. 297(2): p. G378-84. www.ncbi.nlm.nih.gov/pubmed/19541924

  Tetri, L.H., et al., Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol, 2008. 295(5): p. G987-95. www.ncbi.nlm.nih.gov/pubmed/18772365

  Mells, J.E., et al., Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Am J Physiol Gastrointest Liver Physiol, 2012. 302(2): p. G225-35. www.ncbi.nlm.nih.gov/pubmed/22038829

  Dowman, J.K, et al., Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle. Am J Pathol, 2014. 184(5):1550-1561. www.ncbi.nlm.nih.gov/pubmed/24650559

  Mells, J.E., et al., Saturated fat and cholesterol are critical to inducing murine metabolic syndrome with robust nonalcoholic steatohepatitis. J Nutr Biochem, 2014. 26(3): p. 285-92. www.ncbi.nlm.nih.gov/pubmed/25577467

• The Fructose, Palmitate, Cholesterol and Trans-Fat (FPC) diet is a recent NASH diet that includes Western and ALIOS model diets to achieve both metabolic and hepatic NASH features within an accelerated time frame. Key features of the FPC diet include 1) a lower Met content than typical rodent diets by decreasing total protein without supplementing sulfur amino acids; 2) choline supplementation is lower than typical but is not considered deficient; 3) high in sucrose (~34% by weight); 4) 1.25% cholesterol; 5) 52% kcal from fat with fat sources including milkfat fat, palmitic acid and hydrogenated vegetable shortening to provide trans-fats. Like the ALIOS model, the FPC model also provides a glucose/fructose solution to the drinking water.

  FPC饮食：果糖、棕榈酸酯、胆固醇和反式脂肪饮食
  果糖、棕榈酸酯、胆固醇和反式脂肪 (FPC) 饮食是最近的 NASH 饮食，包括西方和 ALIOS 模型饮食，以在加速的时间范围内实现代谢和肝脏 NASH 特征。 FPC 饮食的主要特点包括 1) 通过减少总蛋白质而不补充含硫氨基酸，Met 含量低于典型啮齿动物饮食； 2) 胆碱补充量低于典型值但不被认为是不足的； 3) 蔗糖含量高（约 34% 重量）； 4) 1.25% 胆固醇； 5) 52% kcal 来自脂肪来源，包括乳脂脂肪、棕榈酸和氢化植物起酥油，以提供反式脂肪。 与 ALIOS 模型一样，FPC 模型也为饮用水提供葡萄糖/果糖溶液。

  Examples:

  • TD.160785 52 kcal/Fat Diet (C16:0, HVO, AMF, Choline/Met)
    

    FPC diet: fructose, palmitate, cholesterol and trans-fat diet

  Research use:

  Male C57BL/6J mice fed the FPC diet and provided a glucose/fructose drinking solution developed insulin resistance and NAFLD with inflammation, hepatocyte death, and fibrosis within 16 weeks.

  研究用途：

  喂食 FPC 饮食并提供葡萄糖/果糖饮用溶液的雄性 C57BL/6J 小鼠在 16 周内出现胰岛素抵抗和 NAFLD，并伴有炎症、肝细胞死亡和纤维化。

  Select References:参考文献

  Wang, X., et al., Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab, 2016. 24(6): p. 848-62. www.ncbi.nlm.nih.gov/pubmed/28068223

  Zhu, C., et al., Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis. Sci Transl Med, 2018. 10(468). www.ncbi.nlm.nih.gov/pubmed/30463916

• Common diets to induce obesity (DIO) can be fed to induce uncomplicated NAFLD. These high fat diets typically contain 40–60% kcal from fat without supplemented cholesterol or cholate. Simple sugars such as sucrose or fructose can also be supplemented via diet or water to progress the fatty liver phenotype. Diets can be in pellet or powder/dough form depending on the formula. Some models require limited physical activity and in those cases diets can be fed inside the cage. For more information see our Diet Induced Obesity page.

  高脂肪饮食
  可以喂食诱发肥胖症 (DIO) 的普通饮食以诱发非复杂性 NAFLD。 这些高脂肪饮食通常含有 40–60% 来自脂肪的大卡，而不含补充胆固醇或胆酸盐。 蔗糖或果糖等单糖也可以通过饮食或水补充，以促进脂肪肝表型。 饮食可以是颗粒或粉末/面团形式，具体取决于配方。 有些模型需要有限的体力活动，在这些情况下，可以在笼子内喂食。 欲了解更多信息，请参阅我们的饮食诱发肥胖页面。

  Examples:

  • • TD.08811 45%kcal Fat Diet (21% MF, 2% SBO)
    • TD.06414 Adjusted Calories Diet (60/Fat)
      

      High fat diets

  Research use:

  In susceptible rodent models, high fat diets are commonly used to induce NAFLD with obesity and insulin resistance common metabolic features associated with NASH in humans. However, the degree of NASH pathology (steatosis, inflammation, and fibrosis) is limited or mild and varies depending on the animal model, length of feeding, and dietary components.

   

Diets to induce severe hepatic NAFLD/NASH without obesity or metabolic

• Atherogenic diets high in fat, cholesterol, and cholate

  Originally formulated to induce mild atherosclerosis in wild-type rodents, high fat diets containing added cholesterol (1 – 1.25%) and cholate (0.5% as sodium cholate or cholic acid) have also been useful in inducing NASH. This diet option includes purified “Western” style diets with increased cholesterol and cholate and also hybrid diets. Hybrid diets were originally developed by Beverly Paigen and colleagues by mixing a natural ingredient mouse diet in a 3:1 ratio with a concentrated purified diet (containing 5% cholesterol and 2% sodium cholate) resulting in a diet containing ~15.8% fat, 1.25% cholesterol, and 0.5% sodium cholate. Although a less refined approach, the hybrid diet is associated with increased gallstone formation and liver damage as compared to similar purified diets.

  饮食可诱发严重的肝脏 NAFLD/NASH，但没有肥胖或代谢
  高脂肪、胆固醇和胆酸盐的致动脉粥样硬化饮食
  最初配制用于在野生型啮齿动物中诱导轻度动脉粥样硬化，含有添加胆固醇（1 – 1.25%）和胆酸盐（0.5% 作为胆酸钠或胆酸）的高脂肪饮食也可用于诱导 NASH。 这种饮食选择包括增加胆固醇和胆酸盐的纯化“西式”饮食以及混合饮食。 混合饮食最初是由 Beverly Paigen 及其同事开发的，通过将天然成分的小鼠饮食以 3:1 的比例与浓缩的纯化饮食（含有 5% 胆固醇和 2% 胆酸钠）混合，从而得到含有约 15.8% 脂肪、1.25 % 胆固醇和 0.5% 胆酸钠。 虽然是一种不太精细的方法，但与类似的纯化饮食相比，混合饮食与增加的胆结石形成和肝损伤有关。

  Examples:

  • • TD.02028 Atherogenic Rodent Diet
    • TD.88051 Cocoa Butter Diet and Purina Mouse Chow
    • TD.09237 15% AMF Diet (1% Chol, 0.5% NaChol)

   

  Research use:

  Atherogenic diets are able to induce varied degrees of NASH with increased hepatic inflammation with early fibrosis observed after ten weeks of feeding. However, the metabolic profile typical in human NASH (obesity with insulin resistance) is not recapitulated in this model with animals typically maintaining similar body weights as control fed groups without the development of metabolic syndrome.

  研究用途：

  致动脉粥样硬化饮食能够诱导不同程度的 NASH，并在喂养 10 周后观察到肝脏炎症增加和早期纤维化。 然而，人类 NASH（伴有胰岛素抵抗的肥胖）中典型的代谢特征在该模型中没有被概括，动物通常保持与对照组相似的体重，而没有代谢综合征的发展。

  Select References: 参考文献

  Nishina, P.M., J. Verstuyft, and B. Paigen, Synthetic low and high fat diets for the study of atherosclerosis in the mouse. J Lipid Res, 1990. 31(5): p. 859-69. www.ncbi.nlm.nih.gov/pubmed/2380634

  Kamari, Y., et al., Lack of interleukin-1alpha or interleukin-1beta inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J Hepatol, 2011. 55(5): p. 1086-94. www.ncbi.nlm.nih.gov/pubmed/21354232

  Kim, D.G., et al., Non-alcoholic fatty liver disease induces signs of Alzheimer’s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model. J Neuroinflammation, 2016. 13: p. 1.
  www.ncbi.nlm.nih.gov/pubmed/26728181

  Madrigal-Perez, V.M., et al., Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia. Int J Clin Exp Med, 2015. 8(12): p. 22477-83. www.ncbi.nlm.nih.gov/pubmed/26885230

  Savransky, V., et al., Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol, 2007. 293(4): p. G871-7. www.ncbi.nlm.nih.gov/pubmed/17690174

  • TD.94149 Amino Acid Control DietMethionine and choline deficient (MCD) diets are amino acid defined rodent diets deficient in methionine and choline, high in sucrose (>40% by weight) with ~10% corn oil by weight. Methionine and choline deficiency decreases fat oxidation and export of fat from the liver. Dietary sucrose is necessary for hepatic lipid accumulation and oxidation. The polyunsaturated fat in corn oil promotes hepatic lipid oxidation.

    蛋氨酸/胆碱缺乏 (MCD) 饮食
    蛋氨酸和胆碱缺乏 (MCD) 饮食是氨基酸定义的啮齿动物饮食，缺乏蛋氨酸和胆碱，蔗糖含量高（> 40% 重量）和约 10% 玉米油重量。 蛋氨酸和胆碱缺乏会降低脂肪氧化和脂肪从肝脏的输出。 膳食蔗糖是肝脏脂质积累和氧化所必需的。 玉米油中的多不饱和脂肪促进肝脏脂质氧化。

    Example:

    • TD.90262 Methionine/Choline Deficient Diet
      

      Methionine/choline deficient (MCD) diets

    Control:

• Research use:

  Steatosis, increased serum alanine aminotransferase (ALT), inflammation, and hepatic fat oxidation has been observed within three weeks of feeding the MCD diet with fibrosis development after six weeks. This dietary model does not produce metabolic syndrome (an aspect of NASH in human models) and progressive weight loss (up to 40%) is associated with the MCD diet feeding.

• 研究用途：

  在喂食 MCD 饮食的三周内观察到脂肪变性、血清丙氨酸氨基转移酶 (ALT) 升高、炎症和肝脏脂肪氧化，六周后出现纤维化。 这种饮食模型不会产生代谢综合征（人体模型中 NASH 的一个方面），并且进行性体重减轻（高达 40%）与 MCD 饮食喂养有关。

•  

   

  Select References: 参考文献

  Pickens, M.K., et al., Dietary sucrose is essential to the development of liver injury in the MCD model of steatohepatitis. J Lipid Res, 2009. 50(10):2072-82. www.ncbi.nlm.nih.gov/pubmed/19295183

  Li, Z.Z., et al., Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem, 2009. 284(9): p. 5637-44. www.ncbi.nlm.nih.gov/pubmed/19119140

  Lee, G.S., et al., Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury. J Lipid Res, 2007. 48(8): p. 1885-96. www.ncbi.nlm.nih.gov/pubmed/17526933

  Vetelainen, R., A. van Vliet, and T.M. van Gulik, Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model. J Gastroenterol Hepatol, 2007. 22(9): p. 1526-33. www.ncbi.nlm.nih.gov/pubmed/17716355

  Leclercq, I.A., et al., Intrahepatic insulin resistance in a murine model of steatohepatitis: effect of PPARgamma agonist pioglitazone. Lab Invest, 2007. 87(1): p. 56-65. www.ncbi.nlm.nih.gov/pubmed/17075577

  Kashireddy, P.R. and M.S. Rao, Sex differences in choline-deficient diet-induced steatohepatitis in mice. Exp Biol Med (Maywood), 2004. 229(2): p. 158-62. www.ncbi.nlm.nih.gov/pubmed/14734794

  Dixon, L.J., et al., Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis. Lab Invest, 2012. 92(5): p. 713-23. www.ncbi.nlm.nih.gov/pubmed/2241106

• Emerging NASH models

  Dietary models of NAFLD/NASH continue to evolve with the goal of more accurately recapitulating both the metabolic and hepatic symptoms of human disease. Commonly researchers are studying the synergistic effects of various NASH dietary features to accelerate progression of the model and severity of liver disease.

  新兴的 NASH 模型
  NAFLD/NASH 的饮食模型继续发展，目标是更准确地概括人类疾病的代谢和肝脏症状。 通常，研究人员正在研究各种 NASH 饮食特征的协同效应，以加速模型的进展和肝病的严重程度。

• Control diets

  The choice of control diet is dependent on the specific research goal. Many researchers choose to compare their NAFLD/NASH diet-fed animals to animals fed a natural ingredient, grain-based diet (also referred to as standard diet or chow). These diets differ in the source and level of nutrients as well as in the presence of non-nutritive factors (such as phytates or phytoestrogens).

  Depending on what your main comparisons are, it may be suitable to have a grain-based diet as your control/reference group. However, making such comparisons limits inferences to dietary patterns versus a specific dietary component. In some cases, such as those studies feeding amino acid defined diets like the MCD model, a matched control diet is recommended given the very different formulations and protein sources of grain-based diets.

  When making inferences about specific nutrients within the diet an ingredient matched, low fat control diet may be necessary. There are many options with different levels and types of fat in addition to different types of carbohydrate ranging from sucrose (highly refined and digestible) to corn starch (refined, but more complex) to resistant starch (refined, but not fully digestible).

  A very basic purified control diet would be AIN-93M TD.94048 or AIN-93G TD.94045 . AIN-93 diets have a moderate amount of sucrose at ~10% with fat from soybean oil providing a healthy fatty acid profile. Learn more about AIN diet formulas.

  Contact a nutritionist for an additional information and control diet recommendations.