Submitted on May 7, 2004
Accepted on December 7, 2004
Effects of copper supplementation on copper absorption, tissue distribution, and copper transporter expression in an infant rat model
Kathryn A Bauerly1, Shannon L Kelleher1, and Bo Lonnerdal1*
1 Department of Nutrition, University of California, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: bllonnerdal{at}ucdavis.edu.
Infants are exposed to variable copper (Cu) intake; Cu in breast milk is low, while infant formulas vary in Cu content, as well as the water used for their preparation. Little is known
about the regulation of Cu absorption during infancy. The objectives of this study were to
determine effects of Cu supplementation on Cu absorption and tissue distribution and the
expression of Cu transporters in an infant rat model. Suckling rat pups were orally dosed with 0,
10, or 25 µg Cu /day. Intestine and liver were collected at d 10 and 20 and Cu concentration,
Ctr1, Atp7A, Atp7B, and MT mRNA and protein levels were measured. 67Cu absorption was
measured at d 10 and 20. Total 67Cu absorption decreased and intestinal 67Cu retention increased
with increased Cu intake. At day 10, intestine Cu concentration, MT mRNA and Ctr1 protein
levels increased with supplementation but no changes in Atp7A or Atp7B levels were observed.
At day 20, intestine Cu concentration was unaffected by Cu supplementation but Ctr1 protein
and Atp7A mRNA and protein levels were higher than in controls. In liver, Cu level reflected
Cu intake at d 10 and d 20. There was a significant increase in Ctr1, Atp7B, and MT mRNA
expression in liver at both ages with Cu supplementation. In conclusion, the ability of suckling
rat pups to tolerate varying amounts of dietary Cu may be due to changes in Cu transporters,
facilitated by transcriptional and post-translational mechanisms. Despite these adaptive changes,
Cu supplementation resulted in elevated alanine aminotransferase (ALT) levels, suggesting a risk
of Cu toxicity with supplementation during infancy.
