Location: Arkansas Children's Nutrition CenterTitle: Trace element status and zinc homeostasis differ in breast and formula-fed piglets
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
|MIOUSSE, ISABELLE - University Arkansas For Medical Sciences (UAMS)|
|MASON, ANDREW - University Of California|
|SHARMA, NEHA - Arkansas Children'S Nutrition Research Center (ACNC)|
|BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)|
|Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/14/2014
Publication Date: 1/1/2015
Citation: Ronis, M.J., Miousse, I.R., Mason, A.Z., Sharma, N., Blackburn, M.L., Badger, T.M. 2015. Trace element status and zinc homeostasis differ in breast and formula-fed piglets. Experimental Biology and Medicine. 240(1):58-66.
Interpretive Summary: It is known that trace metals play an important role in biological functions in early development and that trace element imbalance (too much or too little) can have adverse health consequences. There are substantial differences in trace metal composition of breast milk and the cow's milk and soy-protein isolates used as the protein source in infant formulas. In addition, absorption of these trace elements from the gut differs depending on breast vs. formula feeding, and so infant formulas are supplemented with many metals such as zinc and iron. The current study examined differences in trace metal levels in the blood after breast, cow's milk formula, or soy-based infant formula feeding in a newborn pig model. Iron levels were much higher in the formula-fed piglets compared to breast-fed piglets, as a result of low iron levels in breast milk and iron supplementation of the formulas. In contrast, even though levels of zinc were similar in breast milk and both the formulas, milk formula-fed piglets had twice the amount of circulating zinc than breast-fed or soy-formula-fed piglets. The higher body zinc levels in cow's milk formula-fed piglets resulted in changes in expression of zinc transport proteins in the gut and liver and increased the expression and zinc content of the zinc binding protein metallothionein in both the gut and liver driven by activation of a zinc-sensing transcription factor protein MTF-1. These data indicate that trace element status differs in breast-fed, cow's milk formula and soy formula-fed piglets and that despite similar levels of dietary supplementation, increased circulating zinc levels in cow's milk formula-fed piglets produce compensatory responses in zinc transport and binding to equalize tissue concentrations.
Technical Abstract: Differences in trace element composition and bioavailability between breast milk and infant formulas may affect metal homeostasis in neonates. In the current study, piglets were fed soy infant formula (Soy), cow's milk formula (Milk), or were allowed to suckle from the sow from PND2 to PND21. Serum iron concentrations were higher in formula-fed compared to breast-fed piglets (P<0.05). Serum zinc values were higher in Milk compared to breast-fed or Soy groups (P<0.05). Zinc transporter Zip4 mRNA was elevated in small intestine of the Soy compared to breast-fed group (P<0.05). Transporter Znt1 mRNA was greater in small intestine of both formula-fed groups and in liver of the Milk compared to the breast-fed group (P<0.05). Metallothionein (MT) Mt1 mRNA expression was higher in small intestine and liver of Milk compared to breast-fed and Soy groups (P<0.05). In liver, MT protein levels and protein bound zinc were also highly elevated in the Milk compared to other groups (P<0.05). mRNA encoding the hepatic zinc-regulated gene Gclc, was higher in the Milk than Soy group (P<0.05). ChIP assay revealed increased binding of the zinc-regulated transcription factor MTF1 to the promoters of hepatic Mt3 and Gclc genes in the Milk compared to the Soy group. These data indicate that trace element status differs in breast-fed, Milk, and Soy piglets and that despite similar levels of dietary supplementation, significant differences in serum zinc after cow's milk formula compared to soy formula consumption results in compensatory changes in expression of zinc transporters, binding proteins, and zinc regulated genes.