Resveratrol Attenuates Liver Inflammation in Non-Alcoholic Fatty Liver Disease by Activating PINK1-Mediated Mitophagy
by
, , , , and
Shujing Tan
1,2
,
Ran Yu
1,2,
Longwei Sun
1,2,
Manman Shen
1,2
,
Juan Framirez Pedroso
3,
Osmani Chacón Chacón
3
,
Chengmin Li
1,2,*
and
Weiguo Zhao
1,2,* 1
Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
2
Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
3
Research Center on Protein Plants and Bionatural Products, No. 902, 7th Avenue, Playa, La Habana 11300, Cuba
*
Authors to whom correspondence should be addressed.
Animals 2026, 16(7), 1022; https://doi.org/10.3390/ani16071022
Submission received: 24 February 2026
/
Revised: 16 March 2026
/
Accepted: 25 March 2026
/
Published: 27 March 2026
(This article belongs to the Section Animal Physiology)
Simple Summary
Our research indicates that resveratrol improves fatty liver disease by enhancing mitophagy, coupled with inhibiting NLRP3-driven inflammation. These findings not only provide new molecular insights into the pathogenesis of bovine fatty liver, but also pave the way for resveratrol-based interventions, and provide a feasible and active strategy to control the disease in dairy cows in the transitional period.
Abstract
Resveratrol (RES) has been shown to exhibit therapeutic efficacy against fatty liver disease. Yet, the molecular mechanisms by which RES ameliorates liver injury remain unclear. The aim of this study was to investigate the therapeutic effect and mechanism of resveratrol in fatty liver disease. It was found that dairy cows with fatty liver exhibit characteristic hepatic pathologies, including ballooning degeneration, lipid accumulation and elevated serum AST and ALT levels. Parallel to these changes, we observed significant upregulation of the NLRP3 inflammasome alongside suppression of mitophagy in the liver. Additionally, it was demonstrated in vitro that resveratrol pretreatment effectively alleviated PA-triggered NLRP3 inflammasome activation and mitochondrial dysfunction. Furthermore, RES’s mitigating effects against NLRP3 inflammation and mitochondrial injury were reversed by suppressing PINK1-medicated mitophagy. In vivo experiments further demonstrated that resveratrol administration attenuated HFD-induced liver injury and lipid accumulation in a mouse model, concurrent with suppressed NLRP3 activation and an increase in mitophagy, further confirming the mechanism identified in vitro. Our findings reveal that RES ameliorates fatty liver injury primarily by inhibiting the NLRP3 inflammasome through PINK1-mediated mitophagy, which provides a potential novel therapeutic strategy for mitigating fatty liver disease.
