ナガシマ ヨウジ   Nagashima, Yoji
  長嶋 洋治
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Lipid-lowering agents inhibit hepatic steatosis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma mouse model.
掲載誌名 正式名:British journal of pharmacology
略  称:Br J Pharmacol
ISSNコード:00071188
掲載区分国外
巻・号・頁 S0014-2999(15),30439-30439頁
著者・共著者 Orime K, Shirakawa J, Togashi Y, Tajima K, Inoue H, Nagashima Y, Terauchi Y.
発行年月 2015/12
概要 Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic
disorders, and the therapeutic strategies for treating NAFLD and non-alcoholic
steatohepatitis (NASH) have not been fully established. In the present study, we
examined whether lipid-lowering agents inhibited the progression of NAFLD and
tumorigenesis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma
model mouse (STAM mice) generated by streptozotocin injection and a high-fat
diet. Seven-week-old STAM mice were divided into groups fed a high-fat diet (Ctl)
or a high-fat diet supplemented with ezetimibe (Ez), fenofibrate (Ff),
rosuvastatin (Rs), ezetimibe plus fenofibrate (EF), or ezetimibe plus
rosuvastatin (ER) for 4 weeks. At the end of the experiments, an oral glucose
tolerance test, an insulin tolerance test, biochemical analyses using serum and
liver, and a histological analysis of liver were performed in 11-week-old STAM
mice. The lipid-lowering agents did not affect the body weight or the casual
blood glucose levels in any of the groups. The serum triglyceride level was
significantly decreased by Ff, Rs, and EF. Glucose tolerance was improved by Ez
and Ff, but none of these agents improved insulin sensitivity. A histochemical
analysis revealed that the lipid-lowering agents, with the exception of Rs,
significantly inhibited the progression of hepatic steatosis. Nonetheless, no
significant changes in the incidence of hepatic tumors were observed in any of
the groups. Lipid-lowering agents inhibited the progression of hepatic steatosis
without suppressing tumorigenesis in STAM mice. Our data has implications for the
mechanism underlying steatosis-independent hepatic tumorigenesis in mice.
DOI 10.1016/j.ejphar.2015.12.043.