Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway
Tianyu Jiang,
Yao Xiao,
Jinfeng Zhou,
Zupeng Luo,
Lin Yu,
Qichao Liao,
Siqi Liu,
Xinyi Qi,
Hao Zhang,
Menglong Hou,
WeiWei Miao,
Batbold Batsaikhan,
Turtushikh Damba,
Yunxiao Liang,
Yixing Li,
Lei Zhou
Affiliations
Tianyu Jiang
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Yao Xiao
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Jinfeng Zhou
College of Animal Science and Technology, Guangxi University, Nanning, 530004, China
Zupeng Luo
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Lin Yu
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Qichao Liao
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Siqi Liu
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Xinyi Qi
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Hao Zhang
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Menglong Hou
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
WeiWei Miao
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Batbold Batsaikhan
Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia; Department of Health Research, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
Turtushikh Damba
School of Pharmacy, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
Yunxiao Liang
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
Yixing Li
College of Animal Science and Technology, Guangxi University, Nanning, 530004, China; Corresponding author.
Lei Zhou
Institute of Digestive Disease, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China; Corresponding authors.
Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.
