Akiko Suzuki, Keisuke Kakisaka, Yuji Suzuki, Ting Wang, Yasuhiro Takikawa, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka 0208505, Japan
Author contributions: Suzuki A performed in vivo and in vitro studies and wrote the paper; Kakisaka K designed the experiments. Suzuki Y and Wang T analyzed the data; Takikawa Y supervised the study and revised the paper; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported byKAKENHI Grant, No. 16K21307.
Institutional animal care and use committee statement: All of the animal experiments were approved by the Animal Care and Use Committee of Iwate Medical University (Morioka, Japan; 25-025).
Conflict-of-interest statement: There is no conflict-of-interest.
Data sharing statement: No additional data are available.
Correspondence to: Keisuke Kakisaka, MD, PhD, Assistant Professor, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru, Iwate, Morioka 0208505, Japan. keikaki@iwate-med.ac.jp
Telephone: +81-19-6515111 Fax: +81-19-6526664
Received: April 5, 2016 Peer-review started: April 6, 2016 First decision: May 12, 2016 Revised: May 24, 2016 Accepted: June 13, 2016 Article in press: June 13, 2016 Published online: July 28, 2016 Processing time: 107 Days and 17 Hours
Core Tip
Core tip: Autophagy is interrupted in both in vivo and in vitro non-alcoholic steatohepatitis (NASH) models, and impaired autophagy is mediated by Run domain Beclin-1 interacting and cysteine-rich containing (Rubicon) protein expression via c-Jun N-terminal kinase phosphorylation. Rubicon expression appears prior to apoptosis and enhances palmitate toxicity in the hepatocytes, and caspase-9 decreases Rubicon at the protein level during lipoapoptosis. Caspase-9 inhibition with Rubicon expression induces both hepatocyte enlargement and endoplasmic reticulum stress accumulation. The present study extends our knowledge on the precise balance between lipoapoptosis and autophagy via Rubicon expression in NASH and reveals a possible pathophysiology of ballooned hepatocytes in NASH.
