Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells

Tae Woo Jung, Hwan Jin Hwang, Ho Cheol Hong, Hae Yoon Choi, Hye Jin Yoo, Sei Hyun Baik, Kyung Mook Choi

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60 Citations (Scopus)


Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - 2014 Jun 25

Bibliographical note

Funding Information:
This research was supported by a Korea University Grant and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012006363 ) (K.M.C.) and by the Brain Korea 21 Project of the Ministry of Education and Human Resources Development, Republic of Korea (K.M.C. and S.H.B.).


  • C-Jun N-terminal kinase
  • ER stress
  • Non-alcoholic fatty liver
  • Proliferator-activated receptor-γ
  • Resolvin D1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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