Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

• Published in: Frontiers in nutrition (Lausanne) Vol. 9; p. 961892
• Main Authors: Zhang, Lijia, Dai, Xuezheng, Wang, Li, Cai, Jingming, Shen, Jie, Shen, Yang, Li, Xianan, Zhao, Yan
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 11.10.2022
• Subjects: high-fat diet; iron overload; lipid metabolism; NAFLD; Nutrition; oxidative stress
• ISSN: 2296-861X; 2296-861X
• DOI: 10.3389/fnut.2022.961892

Background/aims Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Iron overload has been implicated in chronic non-communicable liver diseases, but its relationship with NAFLD remains unclear. This study aimed to investigate the underlying roles of iron overload in the development of NAFLD. Methods Male Sprague Dawley rats were fed with a high-fat diet (HFD) and/or iron for 8, 12, and 20 weeks. Some rats fed with HFD plus iron also received intraperitoneal injection of deferoxamine (DFO) for 8 weeks. Liver steatosis, lipid metabolism and injury were evaluated. Results A NAFLD model, including typical liver steatosis, was established by feeding rats with a HFD, while iron overload alone is not enough to induce severe NAFL. Compared with rats fed a HFD, excess iron further increased lipid accumulation, serum levels of lipids, enzymes of liver function, and expression levels of CD36 and FAS in rat liver. In addition, iron overload decreased the activities of antioxidative enzymes in liver compared with HFD rats. The levels of CPT1 and the ratios of p-ACC/ACC were also decreased by iron overload. DFO effectively reversed the abnormal lipid metabolism and liver damage induced by a high-fat, high-iron diet. Conclusion A HFD plus iron overload might synergistically aggravate lipid metabolism disorders, liver injury, and oxidative damage, compared with a HFD alone. DFO might help to alleviate lipid metabolism dysfunction and improve the pathogenesis of NAFLD.