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.

Examples:

• TD.88137Adjusted Calories Diet (42% from fat)
• TD.9612121％MF，1.25％CHOL。饮食
• TD.12052842% Kcal/Fat Diet (Incr. Sucrose, 1.25% Chol.)

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.

Select References:

Charlton，M.等人，快餐饮食鼠标：新型小动物模型的纳什膨胀，渐进性纤维化，对人体状况的高生理保真度。AM J Physiol Gastropeptest肝脏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

李，Z.Z.等，非酒精性脂肪肝病中的肝脂分配和肝损伤：硬脂酰-CoA去饱和酶的作用。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.等人，Caspase-1作为高脂肪饮食诱发的非酒精脱脂性肝炎的中央调节器。Plos一个，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 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.

Examples:

• TD.06303.22% HVO Diet
• TD.12033022% HVO + 0.2% Cholesterol Diet
• TD.130885.阿里奥斯加糖糖

Research use:

Alios模型在16周内开发胰岛素抵抗，ALT水平升高，ALT水平升高，脂肪变性。在6个月内观察到增加炎症和早期发育纤维化。纤维化和炎症的严重脂肪变性在饲养的12个月内发育，据报道，伴随着50％的老鼠开发了肝脏肿瘤。将胆固醇（0.2％）加入美国快餐饮食可能加速纳什表型开发。

Select References:

Koppe，S.W.等，反式脂肪饲料导致血清丙氨酸氨基转移酶和胰岛素抗性增加，与标准鼠高脂饮食相比。AM J Physiol Gastropectest 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.等人，GLP-1模拟，黎射蛋白质，改善C57BL / 6J小鼠中的肝脏脂肪变性和心脏肥厚。AM J Physiol Gastropectest肝脏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

梅尔斯，J.E.等人，饱和脂肪和胆固醇对诱导鼠代谢综合征具有鲁棒的非酒精性脱脂性肝炎至关重要。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.

Examples:

• TD.16078552 kcal/Fat Diet (C16:0, HVO, AMF, Choline/Met)

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.

Select References:

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.

Examples:

• TD.08811SBO MF千卡脂肪45% (21%,2%)
• TD.06414Adjusted Calories Diet (60/Fat)

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.

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.

Examples:

• TD.02028致动脉粥啮齿动物饮食
• TD.88051可可脂肪饮食和purina老鼠咸菜
• TD.0923715% AMF Diet (1% Chol, 0.5% NaChol)

Research use:

血液发生饮食能够在喂养10周后观察到的早期纤维化的肝脏炎症增加了多种肿瘤。然而，在这种模型中，在这种模型中典型的代谢谱（肥胖症）在这种模型中，通常在没有代谢综合征的情况下保持类似的体重作为对照组组的动物。

Select References:

Nishina，下午，J.Verstuyft，以及B. Paigen，合成低，高脂饮食，用于研究小鼠的动脉粥样硬化。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.等。，对非甾体抗炎药物有用的临床前分析，用于同时防止胫骨肝炎，动脉粥样硬化和高脂血症。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

Methionine 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.

Example:

• TD.90262Methionine/Choline Deficient Diet

Control:

• TD.94149氨基酸控制饮食

Research use:

在喂养MCD饮食的三周内，在六周后喂养MCD饮食的三周内，已经观察到脂肪变性，增加血清丙氨酸氨基转移酶（ALT），炎症和肝脂肪氧化。这种膳食模型不会产生代谢综合征（人类模型中纳什的一个方面），并且逐步减肥（高达40％）与MCD饮食饲料有关。

Select References:

Pickens，M.K.等人，膳食蔗糖对于Sohopatisitis的MCD模型中肝损伤的发展至关重要。J Lipid Res，2009. 50（10）：2072-82。www.ncbi.nlm.nih.gov/pubmed/19295183

李，Z.Z.等，非酒精性脂肪肝病中的肝脂分配和肝损伤：硬脂酰-CoA去饱和酶的作用。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.，等，Caspase-1介导的饮食脂肪性肝炎中纤维发生调节。实验室投资，2012年92（5）：p。713-23。www.ncbi.nlm.nih.gov/pubmed/22411067

NAFLD / NASH的饮食模型继续发展，目标是更准确地重新承载人类疾病的代谢和肝脏症状。通常研究人员正在研究各种尿液膳食特征的协同效应，以加速肝病模型和严重程度的进展。

A Teklad nutritionist can work with you to formulate new diets in order to investigate novel dietary models of NAFLD/NASH. Contact a nutritionist ataskanutritionist@envigo.comfor a diet consultation.

控制饮食的选择取决于具体的研究目标。许多研究人员选择将他们的NAFLD / NASH饮食喂食动物与喂养天然成分，基于谷物饮食（也称为标准饮食或味道）的动物进行比较。这些饮食在营养素的来源和水平中不同以及在非营养因子（例如植物或植物雌激素）的存在中。

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.

当对饮食中的特定营养素进行推迟时，可能需要低脂肪控制饮食。除了从蔗糖（高度精炼和消化）到玉米淀粉（精制，但更复杂）的不同类型的碳水化合物，还有许多水平和类型的脂肪选择。

A very basic purified control diet would be AIN-93MTD.94048or AIN-93GTD.94045。AIN-93饮食在〜10％的蔗糖中具有中等量的蔗糖，来自大豆油提供健康的脂肪酸谱。学习更多关于AIN diet formulas。

联系a nutritionistfor an additional information and control diet recommendations.