Effects of dietary zinc oxide levels on the metabolism of zinc and copper in weaned pigs

Lay Summary Zinc oxide (ZnO) is commonly used in post-weaning pig diets as growth promoter alternative to antibiotics to prevent diarrhea. The use of supranutritional levels of ZnO in post-weaning pigs diets has been challenged due to environmental issues and concerns related to bacterial resistance to antibiotics and heavy metals. However, the limited knowledge of the consequences of high levels of dietary ZnO on the metabolism of trace minerals has hampered advances to replace this nutritional strategy without compromising piglets health. Therefore, this experiment was conducted to evaluate the effects of increasing levels of dietary ZnO (i.e., 100, 1,000, and 3,000 mg/kg) on Zn and Cu metabolism in weaned piglets. In this experiment, it was demonstrated that systemic Zn levels were not effectively regulated with supplementation levels at 3,000 mg of ZnO/kg of diet. In addition, this level of dietary ZnO increased the intestinal intracellular sequestration of Cu and impaired its renal reabsorption, negatively impacting hepatic, and systemic serum Cu concentrations. These results emphasize the potential risk of Cu deficiency under long-term supranutritional supplementation of dietary ZnO during the post-weaning period, with potentially detrimental impacts on piglets growth. Supranutritional levels of zinc oxide (ZnO) in piglets post-weaning diets are related to environmental concerns and antibiotic resistance issues but the effects on trace minerals metabolism are less explored. This study shows the disturbed homeostasis of zinc and copper in post-weaning piglets fed high levels of ZnO, with a potential risk of Cu deficiency under long-term supranutritional supplementation and detrimental impacts on piglets growth. This study compared different dietary zinc oxide (ZnO) levels on zinc (Zn) and copper (Cu) metabolism in weaned pigs. One hundred twenty weaned piglets (7.96 +/- 1.17 kg; 21 d of age) were used in a completely randomized 3 x 4 factorial design composed with three levels of dietary ZnO at 100 (100Zn), 1,000 (1,000Zn), or 3,000 mg/kg (3,000Zn) and four ages at slaughter at 21 (day 21), 23 (day 23), 35 (day 35), and 42 d (day 42). Dietary Cu levels were constant at 130 mg/kg. Serum, jejunum, liver, and kidney levels of Zn and Cu as well as mRNA abundance of genes related to Zn and Cu metabolism were analyzed. Zinc levels were greatest in 3,000Zn piglets from day 35 in all tissues (P <= 0.01). In 3,000Zn piglets, mRNA expression of ZIP4 was reduced in jejunum whereas ZnT1 and MT3 were stimulated in jejunum and liver and MT1 in kidney (P <= 0.04) from day 35. Copper levels were greatest in jejunum (P = 0.06) and kidney (P <= 0.01; days 35 and 42 only) and lowest in liver and serum (P <= 0.01) of 3,000Zn piglets. In conclusion, the treatment containing 3,000 mg ZnO/kg triggered Zn homeostatic mechanisms in weaned pigs and impaired Cu metabolism through high enterocyte and kidney Cu sequestration.