• Yeon Ji Chae, Dae Won Jun, Waqar Khalid Saeed, Hyeon Tae Kang, Ju Hee Oh, Seung Min Lee, and Kiseok Jang.
• Department Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Korea.
• J. Korean Med. Sci. 2019 Jan 14; 34 (2): e14.

BackgroundThe heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models.MethodsHeterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed.ResultsAt 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes.ConclusionThe diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.

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