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Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress
Author(s) -
Zhang Tian,
Yan Junkai,
Wang Nan,
Dai Lina,
Wang Ying,
Cai Wei
Publication year - 2019
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1002/jpen.1173
Subject(s) - autophagy , unfolded protein response , endoplasmic reticulum , steatosis , hepatocyte , chop , biology , terminal deoxynucleotidyl transferase , endocrinology , medicine , apoptosis , oxidative stress , tunel assay , microbiology and biotechnology , biochemistry , in vitro
Background The objectives of this study were to address the role of autophagy in the pathogenesis of parenteral nutrition (PN)‐associated liver disease (PNALD) and its possible mechanism in vivo. Methods Five‐week‐old male Sprague Dawley rats were fed Shoobree chow (Xietong Organism, Jiangsu, China) and administered intravenous 0.9% saline (sham group), PN (PN group), PN plus rapamycin (1 mg/kg; PN + Rapa group), or rapamycin (Rapa group) for 7 days. Before and after study, body weight, biochemical indicators, hepatic histology, level of autophagy, hepatocyte apoptosis, reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress indicators including binding immunoglobulin protein (BIP), spliced X‐box‐binding protein‐1 (sXBP1), and CCAAT‐enhancer‐binding protein homologous protein (CHOP) were measured. Results Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved‐caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress‐related protein markers, such as BIP, sXBP1 and CHOP. Conclusions Autophagy was suppressed in the PNALD model. Rapamycin treatment induced autophagy and protected against PNALD, possibly by suppressing ROS‐induced ER stress.