4. 今後の展望について

　ヒトと実験動物の肝機能や肝疾患における病態の種差は古くからよく研究されており、実験動物で得た成果をヒトに外挿する際に必ず考慮しなければなりません。また動物実験の削減や代替の視点からも、ヒト由来の細胞を用いたオルガノイドや組織チップがNAFLD/NASHの病態解明や治療薬の開発に使用される機会が今後増えていくと考えられます[15]。一方で、NAFLD/NASHは臓器間の相互作用が病態の発症や進行に関係する慢性の疾患であることから、現状では培養モデルでの検討に限界があります。目的に応じた病態モデルを取捨選択し、有効に活用していくことがNAFLD/NASH克服に必要と考えられます。

参考文献

1.        Akiyama, K., Warabi, E., Okada, K., Yanagawa, T., Ishii, T., Kose, K., Tokushige, K., Ishige, K., Mizokami, Y., Yamagata, K., Onizawa, K., Ariizumi, S. I., Yamamoto, M. and Shoda, J. 2018. Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis. Exp. Anim. 67: 201–218.

2.        Arsov, T., Larter, C. Z., Nolan, C. J., Petrovsky, N., Goodnow, C. C., Teoh, N. C., Yeh, M. M. and Farrell, G. C. 2006. Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. Biochem. Biophys. Res. Commun. 342: 1152–1159.

3.        Bergheim, I., Weber, S., Vos, M., Krämer, S., Volynets, V., Kaserouni, S., McClain, C. J. and Bischoff, S. C. 2008. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: Role of endotoxin. J. Hepatol. 48: 983–992.

4.        Eberlé, D., Hegarty, B., Bossard, P., Ferré, P. and Foufelle, F. 2004. SREBP transcription factors: Master regulators of lipid homeostasis. Biochimie. 86: 839–848.

5.        Eng, J. M. and Estall, J. L. 2021. Diet-induced models of non-alcoholic fatty liver disease: Food for thought on sugar, fat, and cholesterol. Cells. 10: 1–16.

6.        Hearn, T. 2019. Hearn2019_Article_ALMS1AndAlströmSyndromeARecess.pdf. 1–17.

7.        Itoh, M., Suganami, T. and Ogawa, Y. 2021. Role of chronic inflammation in the pathogenesis of nonalcoholic steatohepatitis: Lessons from a unique mouse model using melanocortin receptor-deficient mice. Endocr. J. 68: 743–749.

8.        Jacobs, A., Warda, A. S., Verbeek, J., Cassiman, D. and Spincemaille, P. 2016. An Overview of Mouse Models of Nonalcoholic Steatohepatitis: From Past to Present. Curr. Protoc. Mouse Biol. 6: 185–200.

9.        Kawashita, E., Ishihara, K., Nomoto, M., Taniguchi, M. and Akiba, S. 2019. A comparative analysis of hepatic pathological phenotypes in C57BL/6J and C57BL/6N mouse strains in non-alcoholic steatohepatitis models. Sci. Rep. 9: 1–13.

10.      Kirsch, R., Clarkson, V., Shephard, E. G., Marais, D. A., Jaffer, M. A., Woodburne, V. E., Kirsch, R. E. and De La M Hall, P. 2003. Rodent nutritional model of non-alcoholic steatohepatitis: Species, strain and sex difference studies. J. Gastroenterol. Hepatol. 18: 1272–1282.

11.      Kulathunga, K., Wakimoto, A., Hiraishi, Y., Yadav, M. K., Gentleman, K., Warabi, E., Sakasai, T., Miwa, Y., Mizuno, S., Takahashi, S. and Hamada, M. 2021. Albino mice with the point mutation at the tyrosinase locus show high cholesterol diet-induced NASH susceptibility. Sci. Rep. 11:.

12.      Legry, V., Van Rooyen, D. M., Lambert, B., Sempoux, C., Poekes, L., Español-suñer, R., Molendi-Coste, O., Horsmans, Y., Farrell, G. C. and Leclercq, I. A. 2014. Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin-resistant high-fat-diet-fed foz/foz mice. Clin. Sci. 127: 507–518.

13.      Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A. and Sudoh, M. 2013. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int. J. Exp. Pathol. 94: 93–103.

14.      Santhekadur, P. K., Kumar, D. P. and Sanyal, A. J. 2018. Preclinical models of non-alcoholic fatty liver disease. J. Hepatol. 68: 230–237.

15.      Soret, P. A., Magusto, J., Housset, C. and Gautheron, J. 2021. In vitro and in vivo models of non-alcoholic fatty liver disease: A critical appraisal. J. Clin. Med. 10: 1–18.

16.      Sudoh, M. and Matsumoto, M. 2014. An approach for anti-fibrotic drug discovery in NASH. Folia Pharmacol. Jpn. 144: 69–74.

17.      Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M. 2016. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 64: 73–84.

18.      Zhong, F., Zhou, X., Xu, J. and Gao, L. 2020. Rodent Models of Nonalcoholic Fatty Liver Disease. Digestion. 101: 522–535.

JALAM教育委員会

• シェア
• シェア