steve By Steven Yeung, M.S..

Several different dietary approaches are commonly used to induce the various stages along the NAFLD spectrum. At Taconic Bioscience, our high fat, high fructose, high cholesterol formula (D09100310) is used to produce the phenotype similar to the AMLN NASH mice. This diet has also been tested by the Danish contract research organization, Gubra, and is also referred to as the Gubra-Amlyin NASH (GAN) diet in the literature. In addition to the development of NASH, it’s been shown that mice on D09100310 develop characteristics of the metabolic syndrome, such as obesity, hypercholesterolemia, and hyperinsulinemia with impaired glucose tolerance. This model has demonstrated good clinical translatability; however, it requires lengthy time on diet (20-30 weeks). Substantial space requirements associated with feeding for this duration also limits the utility of D09100310.

Taconic compared the disease progression of their off-the-shelf (OTS) Taconic AMLN mouse to internally grown mice (IG). OTS mice (C57BL/6N) arrived from Taconic at 16, 24 and 32 weeks on D09100310 or a grain based chow. IG mice (C57BL/6N) arrived at 4 weeks of age and at 6 weeks they started on a grain based chow or D09100310. 

The OTS can serve as a reliable metabolically-driven NASH model. The OTS mice develop all the hallmarks of NASH (steatosis, inflammation and fibrosis) however, development of the NASH phenotype in OTS mice is not as severe as the phenotypic characteristics typically observed in internally grown mice (IG). Other potential drawbacks of the OTS model include shipping stress, as well as reductions in body weight and liver function tests. Longer acclimation as well as thermoneutral housing conditions tend to mitigate shipping-induced stress, however, and can promote earlier disease progression. Metabolic NAFLD (or MAFLD) produced by this diet is now being widely used to screen different therapeutic options for this disease and also to learn more about its pathophysiology. When designing your study, it is important to evaluate and select appropriate acclimation strategies, based on the particular needs of your research plan.

We have several diets that are commonly used to induce different stages of NAFLD. Please send us a message if you’re interested in learning more about the other diets and we can help you decide the best diet to use.

References:
Poster - Comprehensive characterization of an off-the-shelf AMLN mouse model and considerations for experimental design in NASH pre-clinical research

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