From Mice to Rats:
Expanding the Application of the GAN Diet (D09100310) in MASH Research
リサーチダイエット社サイエンティストからの最新情報
From Mice to Rats:Expanding the Application of the GAN Diet (D09100310) in MASH Research
Posted on September, 2025 by Jia-yu Ke, Ph.D.
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 代謝異常関連脂肪性肝疾患(MASLD) 代謝異常関連脂肪肝炎(MASH) 脂肪肝 肝炎 肝線維化 ラット(Sprague Dawley・Wistar)
The Research Diets D09100310—commonly known as the GAN diet—is a high-fat, high-fructose, and high-cholesterol formula designed to induce metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) in rodents. While extensive data supports its use in mice — with one study ranking it as the most relevant dietary model for human MASH (1) — its effects in rats have been less explored.
Here, we summarize findings from three recent publications that highlight a clear, time-dependent progression of liver disease in rats fed D09100310.
8 Weeks: Simple Steatosis
In a study by Li et al. (2) Sprague Dawley rats were fed D09100310 or its matched control (D09100304) for 8 weeks. At this early timepoint, rats developed simple steatosis characterized by:
• Elevated Hepatic Triglycerides: A significant increase in liver fat content was observed,
alongside a trend of increased plasma AST and ALT.
• Pronounced Steatosis: H&E staining revealed large lipid vacuoles in the liver.
• No Inflammation or Fibrosis: The expression of key inflammatory (TNF-α) and fibrotic (ACTA2)
markers remained unchanged compared to controls.
12 Weeks: Steatosis with Inflammation
Aldiss et al. (3) fed Wistar rats D09100310 for 12 weeks, revealing disease progression. Key outcomes included:
• Metabolic Changes: Rats exhibited increased body weight gain, liver weight, and adipose depot
mass. Plasma AST, ALT, and cholesterol were all significantly elevated.
• High NAFLD Activity Score (NAS): Rats developed moderate MASLD, with over 56% achieving a NAS
of ≥4. This increase was driven primarily by steatosis and lobular inflammation, while hepatocyte
ballooning was seen in less than 20% of animals.
• Absence of Fibrosis: Despite clear inflammation and steatosis, no liver fibrosis was detected by
histological staging or markers.
16 Weeks: Steatosis, Inflammation, and Fibrosis
Extending the feeding period to 16 weeks in Sprague Dawley rats induced a complete MASH phenotype, as reported by Ren et al. (4). The findings included:
• Systemic Metabolic Dysfunction: Rats showed impaired glucose tolerance and insulin
resistance, classic hallmarks of advanced metabolic disease.
• Elevated Biomarkers: Serum ALT/AST, liver triglycerides, and cholesterol were all significantly
elevated.
• Confirmed Fibrosis: A comprehensive panel of histological stains (H&E, Oil Red O, Sirius Red,
and Masson's trichrome) confirmed the presence of steatosis, inflammation, and the onset of fibrosis.
These studies collectively suggest that wild-type rats progress to fibrosis more rapidly on D09100310 than mice, which typically require over 20 weeks to develop a similar phenotype.
With the resurgence of rat models, driven by advances in genetic engineering, D09100310 offers a valuable and potentially accelerated platform for studying MASH pathogenesis and evaluating new therapies. While more validations are needed, this faster timeline could be a significant advantage for researchers, making the GAN-fed rat a compelling and translational model for human MASH.
References:
- 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. doi:10.1038/s42255-024-01043-6
- Li Y, Chen L, Sottas C, Patel ND, Raul MC, Papadopoulos V. Tspo Depletion Exacerbates Steatosis Through Fatty Acid Uptake. J Cell Mol Med. 2025;29(7):e70500. doi:10.1111/jcmm.70500
- Aldiss P, Nielsen MH, Burm H, et al. FGF21 deletion mildly exacerbates hepatic dysfunction in GAN diet and alcohol fed rats. NPJ Metab Health Dis. 2025;3(1):21. Published 2025 May 28. doi:10.1038/s44324-025-00062-5
- Ren M, Xia Y, Pan H, Zhou X, Yu M, Ji F. Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways. Hepatol Commun. 2025;9(2):e0615. Published 2025 Jan 16. doi:10.1097/HC9.0000000000000615
お問合せはこちらまで
