RAGE promotes dysregulation of iron and lipid metabolism in alcoholic liver disease

• DOI: 10.1016/j.redox.2022.102559
• Publication Date: 2022-12-01T01:41:09Z
• Authors: Yunjia Li; Mengchen Qin; Weichao Zhong; Chang Liu; Guanghui Deng; Menghan Yang; Junjie Li; Haixin Ye; Hao Shi; Chaofeng Wu; Haiyan Lin; Yuyao Chen; Shaohui Huang; Chuying Zhou; Zhiping Lv; Lei Gao
• Keywords: RAGE; Steatosis

Alcoholic liver disease (ALD) is associated with hepatic inflammatory activation and iron overload. The receptor for advanced glycation end products (RAGE) an important metabolic mediator during the development of ALD. aim this study was to determine effect RAGE on homeostasis in We found increased circulating transferrin, hepcidin ferritin ALD patients positively correlated level. knockout (RAGE-/-) wild-type mice were subjected chronic alcoholic feeding 6 weeks induce ALD, inhibitor, chelator or lipid peroxidation inhibitor administered. showed that alcohol administration triggered steatosis, inflammation, oxidative stress, which eliminated by deficiency inhibition RAGE. Surprisingly, pathways metabolism significantly altered, including uptake (Tf/TfR) storage (Ferritin), as well decreased export (FPN1/Hepcidin). In vitro experiments confirmed had different effects mechanism hepatocytes macrophages respectively. conclusion, our data revealed preclinical evidence effective intervention alleviating alcohol-induced injury.