Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by trans-fatty acid plus fructose

• Morinaga Maki

  Department of Gastroenterology, Juntendo University School of Medicine

• Kon Kazuyoshi

  Department of Gastroenterology, Juntendo University School of Medicine

• Saito Hiroaki

  Department of Gastroenterology, Juntendo University School of Medicine

• Arai Kumiko

  Department of Gastroenterology, Juntendo University School of Medicine

• Kusama Hiromi

  Department of Gastroenterology, Juntendo University School of Medicine

• Uchiyama Akira

  Department of Gastroenterology, Juntendo University School of Medicine

• Yamashina Shunhei

  Department of Gastroenterology, Juntendo University School of Medicine

• Ikejima Kenichi

  Department of Gastroenterology, Juntendo University School of Medicine

• Watanabe Sumio

  Department of Gastroenterology, Juntendo University School of Medicine

書誌事項

タイトル別名

• Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by <i>trans</i>-fatty acid plus fructose

抄録

Excess consumption of trans-fatty acid could increase the risk of non-alcoholic steatohepatitis (NASH); however, treatment targeting trans-fatty acid-induced NASH has not been examined. Here we focused on the influence of trans-fatty acid intake on endoplasmic reticulum (ER) stress in hepatocytes, so we investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA), on trans-fatty acid-caused steatohepatitis using diabetic KK-A^y mice. Elaidic acid (EA, trans-fatty acid) alone did not cause definitive liver injury. In contrast, EA plus low-dose fructose induced extensive apoptosis in hepatocytes with severe fat accumulation. EA plus fructose significantly increased ER stress markers such as glucose-regulated protein 78 (GRP78), eukaryotic initiation factor 2α (eIF2α) and phosphorylated c-jun N-terminal kinase (JNK), while PBA significantly reduced this response. In vitro, EA promoted expression of GRP78 and phosphorylation of eIF2α in primary-cultured hepatocytes. EA also increased hepatocellular susceptibility to low-dose tert-butyl hydroperoxide. Treatment with PBA significantly reduced these responses. In conclusion, EA potentiates susceptibly to non-hazardous dose of fructose, and increases ER and oxidative stress. PBA improved steatohepatitis induced by EA plus fructose through amelioration of ER stress. Therefore, ER stress-targeted therapy using a chemical chaperone is a promising novel strategy for trans-fatty acid-induced steatohepatitis.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 57 (3), 183-191, 2015

  一般社団法人　日本酸化ストレス学会

キーワード

• non-alcoholic steatohepatitis
• <i>trans</i>-fatty acid
• endoplasmic reticulum stress
• fructose
• 4-phenylbutyric acid

詳細情報

• CRID: 1390001204672102528
• NII論文ID: 130005106455
• DOI: 10.3164/jcbn.15-75
• ISSN: 18805086
• ISSN: 09120009
• Web Site: https://www.jstage.jst.go.jp/article/jcbn/57/3/57_15-75/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016232526
• 本文言語コード: en
• データソース種別:
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  • Crossref
  • CiNii Articles
  • KAKEN
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