Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet
スポンサーリンク
概要
- 論文の詳細を見る
著者最終稿を登録可能.Recently, nonalcoholic steatohepatitis (NASH) was found to be correlated with cardiovascular disease events independently of the metabolic syndrome. The aim of this study was to investigate whether an atherogenic (Ath) diet induces the pathology of steatohepatitis necessary for the diagnosis of human NASH and how cholesterol and triglyceride alter the hepatic gene expression profiles responsible for oxidative stress. We investigated the liver pathology and plasma and hepatic lipids of mice fed the Ath diet. The hepatic gene expression profile was examined with microarrays and real-time polymerase chain reactions. The Ath diet induced dyslipidemia, lipid peroxidation, and stellate cell activation in the liver and finally caused precirrhotic steatohepatitis after 24 weeks. Cellular ballooning, a necessary histological feature defining human NASH, was observed in contrast to existing animal models. The addition of a high-fat component to the Ath diet caused hepatic insulin resistance and further accelerated the pathology of steatohepatitis. A global gene expression analysis revealed that the Ath diet up-regulated the hepatic expression levels of genes for fatty acid synthesis, oxidative stress, inflammation, and fibrogenesis, which were further accelerated by the addition of a high-fat component. Conversely, the high-fat component down-regulated the hepatic gene expression of antioxidant enzymes and might have increased oxidative stress. Conclusion: The Ath diet induces oxidative stress and steatohepatitis with cellular ballooning. The high-fat component induces insulin resistance, down-regulates genes for antioxidant enzymes, and further aggravates the steatohepatitis. This model suggests the critical role of lipids in causing oxidative stress and insulin resistance leading to steatohepatitis. Copyright © 2007 by the American Association for the Study of Liver Diseases
論文 | ランダム
- 膵臓に発生した primitive neuroectodermal tumor の一例
- 乳児肥厚性幽門狭窄症における硫酸アトロピン静注療法の臨床的検討
- E65 嚢胞性肺疾患での、LT比計測の有用性(横隔膜ヘルニア(2)・肺)
- E59 先天性横隔膜ヘルニア症例に対するECMO開始基準値の検討(横隔膜ヘルニア(1))
- C85 肥厚性幽門狭窄症に対する硫酸アトロピン療法 : 超音波検査による幽門筋の観察(胃・幽門狭窄)