@article{oai:kanazawa-u.repo.nii.ac.jp:00013288,
 author = {Kurita, Seiichiro and Takamura, Toshinari and Ota, Tsuguhito and Matsuzawa-Nagata, Naoto and Kita, Yuki and Uno, Masafumi and Nabemoto, Satoko and Ishikura, Kazuhide and Misu, Hirofumi and Ando, Hitoshi and Zen, Yoh and Nakanuma, Yasuni and Kaneko, Shuichi},
 issue = {2-3},
 journal = {European Journal of Pharmacology},
 month = {Jul},
 note = {Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-β, α1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis. © 2008 Elsevier B.V. All rights reserved., 金沢大学大学院医学系研究科, 金沢大学医薬保健研究域医学系},
 title = {Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects},
 volume = {588},
 year = {2008}
}