Translational Taconic Model Excels in Recapitulating Human Liver Disease (MASLD)

Published: August 27, 2024

Key TakeawaysKey Takeaways

  • A recent study published in Nature Metabolism validated Taconic's Diet-Induced NASH B6 as a translational model recapitulating key features of MASLD, including fibrosis and metabolic dysfunction, making it a robust preclinical tool.
  • Researchers developed a human proximity score to evaluate nearly 40 mouse and rat models, finding Taconic's NASH B6 mice to excel in mirroring human MASLD characteristics.
  • Taconic’s NASH B6 mice not only mirrored human MASLD progression, but also responded well to therapeutic interventions, making them invaluable for both understanding the underlying disease and for developing novel therapeutic options.

 

A recent study published in Nature Metabolism provided an unbiased comparison of various mouse and rat models in terms of their ability to reflect the progression of metabolic dysfunction-associated liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH). The study found that Taconic’s models exhibit key features of MASLD, including fibrosis and metabolic dysfunction.

This research represents a significant step forward in validating effective models for MASLD and further demonstrates the critical importance of translatable MASLD models in novel therapeutic discovery and development.

Understanding MASLD and Its Complexity

MASLD is associated with conditions such as obesity, type II diabetes, dyslipidemia, cancer, atherosclerosis, and insulin resistance. Previously known as nonalcoholic fatty liver disease (NAFLD), MASLD progresses through multiple stages: from steatosis (fatty liver) to steatohepatitis (MASH), which is marked by inflammation and scarring, and ultimately to cirrhosis, where liver cells are replaced by fibrotic tissue, leading to liver failure. The risk of hepatocellular carcinoma increases as the disease progresses.

Despite the availability of over different 500 mouse and rat models attempting to replicate human MASLD, no single model fully mimics all aspects of the disease. Various approaches, including special diets and chemical induction, simulate different stages of MASLD. While genetically engineered models can provide insights into obesity and comorbidities, the complexity of MASLD and the the lack of validated translational models present significant challenges in study design.

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Diet Induced NASH B6

Taconic is the first and only vendor to offer a diet-induced NASH model off the shelf.
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Evaluating Models Using an Unbiased Human Proximity Score

In a large-scale comparison, researchers from the University of Cambridge, Newcastle University, the European Bioinformatics Institute, and the LITMUS consortium developed a human proximity score to assess how closely nearly 40 mouse and rat models replicate human MASLD characteristics. Taconic’s NASH mice performed exceptionally well in this evaluation.

The researchers assessed models across three categories:

  1. Obesity and/or metabolic syndrome
  2. Development of steatohepatitis with progressive fibrosis
  3. Similarity of histological and molecular features to human MASH

They created a human proximity score by integrating metabolic phenotype data, liver histopathology, and liver transcriptome data, using human disease as a reference.

Taconic Mouse Models Excel in Modeling Human MASLD

The study concluded that, while genetically modified and chemically induced models are convenient, they do not adequately replicate human MASLD for preclinical research. In contrast, Taconic's C57BL6/NTac NASH mice fed the Gubra Amylin Diet (containing 40 kcal% fat, 20 kcal% fructose, and 2% cholesterol)—referred to by the authors as GAN-C2 mice—excelled in mirroring the disease’s progression and key underlying features. GAN-C2 mice achieved high scores in the NAFLD [MASLD] activity score (NAS), reflecting severe disease characteristics such as steatosis, ballooning, and liver inflammation. Notably, GAN-C2 mice also mirrored metabolic changes seen in human MASLD.

“In our evaluation of various study designs, the most effective was observed with the GAN-C2 diet fed to C57BL6/NTac [Taconic NASH B6] or ob/ob mice.” 1

 

Clinical Translatability and Research Implications

The GAN-C2 model [Taconic NASH B6] not only reflected key aspects of MASLD but also responded well to therapeutic interventions, leading to a reduction in weight, improved dyslipidemia, and reduced damage to the liver. This model is particularly valuable for researchers looking for a more highly translatable MASLD/MASH model for basic research and the development of novel therapeutics. It is also useful for evaluating dietary interventions similar to those used in human treatments.

Read the full paper here

Taconic is the first and only vendor to offer a study-ready inventory of C57BL/6NTac male mice conditioned on a modified Amylin NASH diet. Connect with a field application scientist to discuss how diet-induced mice can advance your next study, or call 1-888-TACONIC (888-822-6642) in the US, +45 70 23 04 05 in Europe, or email info@taconic.com.

1. Vacca M, Kamzolas I, Harder LM, et al. An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nat Metab. 2024;6(6):1178-1196. https://doi:10.1038/s42255-024-01043-6

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Histopathological Characterization of the Diet Induced NASH B6

Nonalcoholic steatohepatitis (NASH) is a complex disease with limited treatment options. To better understand disease pathogenesis and to develop new therapies, researchers need translational preclinical animal models. In this webinar, we will review rodent models of NASH, focusing on Taconic Biosciences’ Diet Induced NASH B6.

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The Diet Induced NASH B6: A Translational NASH Model for Drug Discovery

Register for the webinar to hear about how Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging public health threats. NAFLD is a common chronic liver disease, with estimates of incidence around 25% worldwide. NASH represents the more severe end of the NAFLD spectrum and there are currently no approved therapeutics to treat NASH.

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