Reducing endoplasmic reticulum stress does not improve steatohepatitis in mice fed a methionine- and choline-deficient diet.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Anne S HenkelRichard M Green

Abstract

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of nonalcoholic steatohepatitis. The ER stress response is activated in the livers of mice fed a methionine- and choline-deficient (MCD) diet, yet the role of ER stress in the pathogenesis of MCD diet-induced steatohepatitis is unknown. Using chemical chaperones on hepatic steatosis and markers of inflammation and fibrosis in mice fed a MCD diet, we aim to determine the effects of reducing ER stress. C57BL/6J mice were fed a MCD diet with or without the ER chemical chaperones 4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) for 2 wk. TUDCA and PBA effectively attenuated the ER stress response in MCD diet-fed mice, as evidenced by reduced protein levels of phosphorylated eukaryotic initiation factor 2α and phosphorylated JNK and suppression of mRNA levels of CCAAT/enhancer binding protein homologous protein, glucose-regulated protein 78 kDa, and X-box binding protein 1. However, PBA and TUDCA did not decrease MCD diet-induced hepatic steatosis. MCD diet-induced hepatic inflammation, as evidenced by increased plasma alanine aminotransferase and induction of hepatic TNFα expression, was also not reduced by PBA or TUDCA. PBA and TUDCA did not ...Continue Reading

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Citations

Dec 20, 2013·BioFactors·Robin P da SilvaRené L Jacobs
Oct 26, 2016·Liver International : Official Journal of the International Association for the Study of the Liver·Annelies ParidaensLindsey Devisscher
Apr 27, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xu XuAnn-Hwee Lee
Feb 27, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Igor P PogribnyIvan Rusyn
Oct 17, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xiaoying LiuRichard M Green
Jan 3, 2018·The Journal of Clinical Investigation·Jonathan A Kropski, Timothy S Blackwell
Oct 25, 2014·Current Pathobiology Reports·Carmen García-RuizJosé C Fernandez-Checa
Jun 24, 2020·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Liyan LiuChanghao Sun

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