High Iron Consumption Modifies the Hepatic Transcriptome Related to Cholesterol Metabolism

Iron supplementation is a common method for alleviating symptoms of iron deficiency, but excessive iron intake may lead to systemic copper deficiencies and hypercholesterolemia. In our study, we explored the intricate relationship between dietary iron and copper levels and their impact on cholesterol metabolism. Using a rat model, we conducted dietary interventions with varying iron and copper concentrations and analyzed hepatic transcriptomes. High iron intake coupled with low copper intake induced hypercholesterolemia and altered the expression of genes associated with cholesterol and lipid metabolism, thereby, exacerbating cardiovascular disease risks. Conversely, copper supplementation mitigated these hepatic gene expression alterations, suggesting that dietary copper plays a role in cholesterol regulation. Transcriptomic analysis revealed significant upregulation of genes involved in cholesterol synthesis and antioxidative pathways in response to high iron intake, while genes involved in cholesterol elimination were downregulated. Furthermore, high iron consumption was associated with cellular apoptosis and the activation of cholesterol synthesis. Our findings underscore the importance of balanced iron and copper intake in cholesterol homeostasis and highlight the potential of copper supplementation for mitigating iron-induced hypercholesterolemia.