RESEARCH DIETS

Choosing the Appropriate Dietary Model for Preclinical Fatty Liver Disease Research

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Keywords
D09100310(高脂肪高フルクトース高コレステロール飼料) GAN飼料 D16022301 (トランス脂肪酸非含有飼料) A06071302(CDAHFD:超高脂肪コリン欠乏メチオニン減量飼料） L10016（Lieber-DeCarli Liquid Diet） ウエスタンダイエット 代謝機能障害関連脂肪性肝疾患（MASLD） 代謝機能障害アルコール関連肝疾患（MetALD） 代謝機能障害関連脂肪肝炎（MASH） インスリン抵抗性 線維化 NIAAAアルコール関連肝疾患モデル アルコール関連肝疾患（ALD）

Choosing the Appropriate Dietary Model for Preclinical Fatty Liver Disease Research: Lessons from the 2026 European Association for the Study of the Liver (EASL) Position Paper

Just before the start of EASL Congress 2026, a new position paper on preclinical models of steatotic liver disease (SLD) was published in the Journal of Hepatology. One of the main messages of the paper is simple: diet composition matters.

SLD includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), metabolic and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD). As these diseases become more common worldwide, researchers need animal models that closely resemble human disease.

Not All Western Diets Are the Same
Many researchers use a "Western diet" to induce fatty liver disease in rodents. However, not all Western diets are the same. They can differ in fat source, cholesterol level, sugar type, choline content, and other nutrients.

These differences can affect body weight, insulin resistance, liver fat accumulation, inflammation, and fibrosis. Because of this, the EASL authors recommend reporting complete diet information, including nutrient composition, manufacturer, and catalog number. This helps improve reproducibility and allows researchers to compare results between studies.

Which Models Best Represent MASLD?
The paper identifies diets high in fat, fructose, and cholesterol as some of the best models for MASLD.  

1. Two commonly used examples are the Gubra Amylin NASH (GAN) diet (Cat# D09100310, Research Diets, Inc.) and the non-trans fat (NTF) diet (Cat# D16022301, Research Diets, Inc.). These diets produce many features seen in patients, including obesity, insulin resistance, dyslipidemia, liver fat accumulation, inflammation, and fibrosis. The GAN diet was also ranked #1 by LITMUS¹ consortium for its human proximity score, a key indicator of clinical translatability.

2. The fructose-palmitate-cholesterol (FPC) diet (Cat# TD.190142, Inotiv, contains trans-fats) is also highlighted as a model that effectively drives metabolic changes and rapid fibrosis. However, its reliance on trans-fats, which are currently banned in numerous countries, reduces its modern utility. Researchers seeking high clinical relevance may prefer non-trans fat alternatives, such as the GAN or NTF diets.

The paper also discusses choline-deficient and methionine-restricted diets, such as the CDAHFD (Cat# A06071302, Research Diets, Inc.). These diets cause rapid liver injury and fibrosis, but the animals remain lean and do not develop the metabolic abnormalities typically seen in MASLD. Therefore, the authors suggest that these models should not be considered true MASLD models.

What About MetALD and ALD?
MetALD is a newer disease category that combines metabolic dysfunction with alcohol consumption. To model this condition, the paper recommends combining a MASLD-inducing diet with chronic ethanol exposure. One example is the DUAL model, which combines a Western diet with ethanol administration. This model produces both metabolic and alcohol-related liver injury and is becoming increasingly popular for MetALD research.

For ALD research, the Lieber-DeCarli liquid diet remains one of the most widely used models of chronic alcohol exposure. For studies focused on alcohol-associated hepatitis, the NIAAA model combines chronic alcohol feeding with an acute binge ethanol challenge.

Key Takeaways
The 2026 EASL position paper reminds us that not all diet models are the same. Choosing the right model depends on the disease being studied and the scientific question being asked. Careful attention to diet composition and model selection can improve study quality, increase reproducibility, and help researchers generate findings that are more relevant to human disease.

Reference

Gallage S, Castro RE, Estall J, et al. EASL position paper on preclinical models of
steatotic liver disease. J Hepatol.
Published online May 27, 2026. doi:10.1016/j.jhep.2026.04.029

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