(P30-020-25) Impact of Extra Dietary Iron on Copper Homeostasis and Cholesterol Metabolism: The Protective Role of Copper Supplementation

Objectives: This study aimed to explore how extra dietary iron intake disrupts copper balance, resulting in copper deficiency, metabolic disturbances, and altered cholesterol metabolism using a rodent model.

Methods: Male Sprague–Dawley rats, aged five weeks were fed modified AIN-93G-based diets with varying iron levels—adequate (~120 μg/g) or high (~7544 μg/g)—and copper levels—low (~0.3 μg/g), adequate (~6 μg/g), or high (~153 μg/g)—for 5 weeks.

Results: Rats on high-iron diets developed anemia, decreased copper concentrations in organs and feces, and shorter colon lengths. Increased iron intake reduced systemic copper distribution, leading to copper deficiency-related disorders; however, these disturbances were mitigated by additional dietary copper. Serum cholesterol levels were significantly affected: high iron intake increased total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, while copper supplementation counteracted these increases. Comparative hepatic transcriptome analysis revealed that rats consuming high-iron and low-copper diets exhibited gene expression changes associated with elevated cholesterol levels during lipid metabolism. Specifically, genes involved in β-oxidation (2,4-DECR, CROT, and carnitine O-acetyltransferase) were downregulated, whereas genes related to cholesterol biosynthesis (17β-HSD7, PCSK9, SQLE, and IPPI) and fatty acid synthesis (FAS and ACSS2) were upregulated. Additional copper supplementation normalized these genetic changes.

Conclusions: Current findings underscore the need for a balanced intake of iron and copper to maintain proper copper levels and support cholesterol regulation. Moreover, dietary copper supplementation may be a viable approach to prevent hypercholesterolemia and metabolic issues caused by excessive iron consumption.

Funding Sources: This work was supported by NRF-2021R1I1A3060357.