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A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Authors:
Takafumi Sakuma Masato Nakamura Tetsuhiro Chiba Terunao Iwanaga Motoyasu Kan Ryuta Kojima Junjie Ao Yaojia Ma Hidemi Unozawa Naoto Fujita Kengo Kanayama Hiroaki Kanzaki Keisuke Koroki Kazufumi Kobayashi Ryo Nakagawa Naoya Kanogawa Soichiro Kiyono Takayuki Kondo Tomoko Saito Sadahisa Ogasawara Shingo Nakamoto Ryosuke Muroyama Jun Kato Takashi Kishimoto Naoya Kato

Lab Invest 2022 May 28. Epub 2022 May 28.

Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-A mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The KK-A mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A prominent accumulation of triglycerides and cholesterol in the liver was observed at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12 weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still developed steatohepatitis and fibrosis. In summary, we established a diet-induced murine NAFLD model with the rapid development of steatohepatitis and fibrosis, bearing obesity and insulin resistance. This model could be useful as preclinical models for drug development of NAFLD.

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http://dx.doi.org/10.1038/s41374-022-00807-6DOI Listing
May 2022

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