期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2015
卷号：57
期号：3
页码：183-191
DOI：10.3164/jcbn.15-75
出版社：The Society for Free Radical Research Japan
摘要：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-Ay 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.
