Ken Sugimoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of General Geriatric Medicine,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Involvement of microsomal triglyceride transfer protein in nonalcoholic steatohepatitis in novel spontaneous mouse model.
Journal Formal name：Journal of hepatology
Abbreviation：J Hepatol
ISSN code：16000641/01688278
Domestic / ForeginForegin
Volume, Issue, Page 52(6),pp.903-912
Author and coauthor Shindo Nobuyasu, Fujisawa Tomomi, Sugimoto Ken, Nojima Koji, Oze-Fukai Aya, Yoshikawa Yuki, Wang Xiang, Yasuda Osamu, Ikegami Hiroshi, Rakugi Hiromi
Publication date 2010/06
Summary BACKGROUND & AIMS:Nonalcoholic fatty liver disease (NAFLD) is currently recognized as a global health issue and encompasses a wide spectrum of entities, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). The lack of a spontaneous animal model of NASH, however, has hampered basic research in this field.METHODS:We examined the hepatic lesions in the inbred Fatty Liver Shionogi (FLS) mouse, which exhibits type 2 diabetes, and investigated the molecular mechanism leading to NAFLD/NASH. Using vector-mediated hepatic expression of microsomal triglyceride transfer protein (MTP), a key molecule for very low density lipoprotein (VLDL) assembly and export, its contribution to the hepatic lesions as well as to glucose intolerance was examined.RESULTS:The FLS mouse, maintained on normal chow, exhibited excessive hepatic triglyceride (TG) accumulation due to impaired VLDL secretion, and subsequently hepatic lesions comparable to NASH, with increased expression of inflammatory molecules as well as insulin resistance. Gene expression and Western blot analyses demonstrated reduced hepatic expression of MTP in the FLS mouse. Hepatic induction of MTP resulted in a reduction in hepatic TG accumulation, improvement of VLDL export, and amelioration of NASH-like lesions, as well as glucose intolerance.CONCLUSIONS:These data suggest that the FLS mouse could serve as a spontaneous model of NASH with insulin resistance, and that reduced MTP is involved in the development of NASH, pointing towards MTP as a critical target for the prevention and treatment of NASH.
DOI 10.1016/j.jhep.2009.12.033
PMID 20392512