Positive : Insights

The so-called “silent” liver disease ofNASHranks third for the leading causes of liver transplants我们的全球肥胖流行病只增加了纳什的患病率。如果没有批准的纳什治疗，医疗保健行业必须探索这种未满足的医疗需求的治疗策略。

非酒精性脂肪肝病（NAFLD）和非酒精脂肪肝炎（NASH）的动物模型已经证明有助于understanding disease progression,developing new treatment options and improving diagnostic techniques. To produce rodent models of NAFLD and NASH,diet manipulation is a useful tool.When choosingdietary features来induce NAFLD pathologies, researchers should consider the animal model, time frame and desired disease outcome.

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

1) Feed rodents for longer periods of time to induce obesity, metabolic syndrome and mild NASH

2）喂养营养缺乏饮食以在相对较短的时间内诱导严重肿瘤的肝功能，而不会诱导代谢症状，例如肥胖和胰岛素抵抗

Exploring these dietary methods in more detail will help you to make informed decisions about the therapeutic strategies available.

Inducing obesity, metabolic syndrome and mild NAFLD/NASH

Western/fast food style diets with milkfat and cholesterol are high in palmitate and sucrose. Dietary palmitate and cholesterol have previously been associated with the progression from simple steatosis to NASH.Thesedietscan 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 after 14 to 20 months.

随着美国生活方式诱导的肥胖综合征（ALIO）模型，提供了“美国快餐”饮食，其在脂肪脂肪和糖中很高。来自氢化植物缩短的反式脂肪与啮齿动物肿瘤模型中的胰岛素抵抗和肝脏炎症增加有关。Alios模型在16周内开发胰岛素抵抗，升高的ALT水平和脂肪变性。早6个月已观察到纤维化的增加和早期发育。After 12 months, mice exhibited severe steatosis with fibrosis and inflammation,50％的小鼠开发出肝脏肿瘤。

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

These diets include Western and ALIOS model diets to achieve both metabolic and hepatic NASH features within an accelerated time frame. These diets have lower methionine and choline content than typical rodent diets, and are high in sucrose. The high milkfat in these diets provide SFA and palmitic acid. Hydrogenated vegetable shortening provides trans-fats. Male mice developed insulin resistance and NAFLD with inflammation, hepatocyte death and fibrosis within 16 weeks of feeding.

In all of the above diets, a glucose/fructose solution can be added to the drinking water, which may further promote NASH development.

Working with high fat diets

These diets typically contain 40 to 60 percent kcal from fat without supplemented cholesterol or cholate. The degree of NASH pathology is limited or mild and varies depending on the animal model, length of feeding and dietary components. For more information, see ourDiet Induced Obesity page.

Inducing more severe hepatic NAFLD/NASH

为了诱导更严重的肝脏NAFLD / NASH没有肥胖或代谢综合征，研究人员有一些选择：

1) Atherogenic diets high in fat, cholesterol and cholate

2）甲硫氨酸/胆碱缺陷（MCD）饮食

Atherogenic diets high in fat, cholesterol and cholate have added cholesterol (1 – 1.25%) and cholate to help induce NASH.这种饮食选择包括纯化的“西方”风格饮食，胆固醇和胆酸盐和杂交饮食，其是一种与浓缩纯饮食的3：1的基团的自然成分小鼠饮食混合。与类似纯化的饮食相比，杂交饮食与胆结石形成和肝损伤有关。致动脉发生饮食诱导随着肝脏炎症增加的多种肿瘤，早期纤维化观察到喂养十周后。

甲硫氨酸/胆碱缺陷（MCD）饮食是氨基酸定义的甲硫氨酸和胆碱的啮齿动物饮食，这降低了脂肪氧化和来自肝脏的脂肪的出口。此外，这些饮食在蔗糖中高，玉米油重量约为10％。在三周内观察到脂肪变性，增加血清丙氨酸氨基转移酶，炎症和肝脂肪氧化，六周后纤维化发育。这种饮食不会产生代谢综合征（这是人类模型中纳什的一个方面），并且与逐步减肥（高达40％）相关。

Control diets

许多研究人员将他们的NAFLD / NASH饮食喂食动物与喂养动物的动物进行比较天然成分，谷物饮食，取决于研究目标。您可以chatwith a nutritionist and obtain additional information and control diet recommendations.

在生产高质量的杂交瘤和MAB时，仔细的规划和制备是至关重要的。通过与经验丰富的合作伙伴合作，研究人员可以消除许多普通陷阱，同时还节省了时间和金钱。

The future of NAFLD/NASH diets

膳食NAFLD / NASH模型continue to evolve.Currently, diets which induce obesity, metabolic syndrome and mild NASH require long term feeding (4 to 12 months) to induce mild fibrosis; often add a glucose/fructose solution to the drinking water and promote sedentary behavior by removing overhead cage feeders. Diets to induce more severe hepatic NASH often do not recapitulate metabolic symptoms associated with NASH such as obesity or insulin resistance and are commonly fed for 3 to 12 weeks to induce hepatic inflammation and early fibrosis.

As research continues to expand, new diets can be formulated to investigate emerging dietary models of NAFLD/NASH and help address this urgent unmet medical need.

Downloadour mini-paper on NAFLD/NASH studies in rodents to learn more about dietary factors.