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タイトル: | Establishment of a new nonalcoholic steatohepatitis model; Ovariectomy exacerbates nonalcoholic steatohepatitis-like pathology in diabetic rats |
著者: | Saigo, Yasuka Sasase, Tomohiko Uno, Kinuko Shinozaki, Yuichi Maekawa, Tatsuya Sano, Ryuhei Toriniwa, Yasufumi Miyajima, Katsuhiro Ohta, Takeshi |
著者名の別形: | 齊郷, 耕佳 篠崎, 雄一 前川, 竜也 鳥庭, 靖文 太田, 毅 |
キーワード: | NAFLD NASH SDT-fatty rats Ovariectomy (OVX) |
発行日: | Jul-2022 |
出版者: | Elsevier BV |
誌名: | Journal of Pharmacological and Toxicological Methods |
巻: | 116 |
論文番号: | 107190 |
抄録: | An increasing number of patients worldwide are being diagnosed with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD/NASH) because of the growing prevalence of obesity and metabolic disorders. The incidence of NAFLD is higher in postmenopausal women than in premenopausal women. The decline in the level of female hormones might have an effect on the deterioration of metabolism. In the present study, we investigated the potential of Spontaneously Diabetic Torii (SDT) fatty rats as a new animal model for NAFLD. We created a menopausal model by ovariectomy (OVX) in female rats. Sprague-Dawley (SD) rats, SDT rats, and SDT-fatty rats were divided into sham and OVX groups and maintained until 40 weeks of age. The results showed that OVX-induced weight gain was observed in SD and SDT rats. In addition, OVX-induced hepatic triglyceride accumulation was increased in all strains, and there was a significant increase in hepatic triglyceride levels in OVX-SDT fatty rats compared to those in Sham-SD rats. Furthermore, liver fibrosis was worsened in the OVX-SDT fatty rats. In addition, OVX-induced increase in blood ALT level was observed in SDT-fatty rats. Gene expression analysis showed OVX-induced upregulation of Srebp1 expression and downregulation of Pemt and Mttp in OVX rats. These results indicate that OVX-SDT fatty rats exhibit NASH with more severe hepatic fibrosis than untreated animals, suggesting that OVX-induced estrogen reduction may have enhanced lipid synthesis in the liver. It is also possible, although hypothetical, that OVX may decrease VLDL secretion, which may more strongly induce NASH. |
著作権等: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ The full-text file will be made open to the public on 1 July 2023 in accordance with publisher's 'Terms and Conditions for Self-Archiving' This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/275413 |
DOI(出版社版): | 10.1016/j.vascn.2022.107190 |
PubMed ID: | 35688322 |
出現コレクション: | 学術雑誌掲載論文等 |
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