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Resveratrol Alleviates Endoplasmic Reticulum Stress–Associated Hepatic Steatosis and Injury in Mice Challenged with Tunicamycin
Author(s) -
Chen Yanan,
Zhang Hao,
Chen Yueping,
Zhang Yuying,
Shen Mingming,
Jia Peilu,
Ji Shuli,
Wang Tian
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000105
Subject(s) - unfolded protein response , steatosis , tunicamycin , endoplasmic reticulum , resveratrol , nonalcoholic fatty liver disease , oxidative stress , liver injury , fatty liver , medicine , endocrinology , steatohepatitis , sirtuin , lipid peroxidation , immunology , pharmacology , chemistry , biology , microbiology and biotechnology , biochemistry , disease , acetylation , gene
Scope Endoplasmic reticulum (ER) stress is widely recognized as a critical factor linked to lipid metabolic disorders in nonalcoholic fatty liver disease. However, its pathogenesis remains elusive, and therapeutic options are limited. This study investigates the potential of resveratrol (RSV) to alleviate hepatic steatosis and injury in a tunicamycin (TM)‐induced murine ER stress model and provides detailed evidence. Methods and Results Male C57BL/6J mice were orally administered either RSV or vehicle for 2 weeks before the TM challenge. Results indicated that TM induced ER morphological damage and severe unfolded protein reaction (UPR), accompanied by increases in lipid accumulation, oxidative damage, and inflammatory response. Administering RSV decreased the expression of ER stress markers, partially normalized the active levels of UPR sensors, and facilitated sirtuin 1 activity in the liver under ER stress. Notably, the TM‐induced hepatic steatosis was also alleviated by RSV, possibly by regulating the expression pattern of genes involving lipid oxidation and delivery. Consistently, RSV attenuated the TM‐induced increases in lipid peroxidation, hepatocyte apoptosis, and the overactivation of inflammatory signals. Conclusion RSV may have an auxiliary therapeutic potential to prevent the development of steatosis and its progression to steatohepatitis in the liver by alleviating severe ER stress.