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United States Department of Agriculture

Agricultural Research Service

Research Project: IMPACT OF EARLY DIETARY FACTORS ON CHILD DEVELOPMENT AND HEALTH

Location: Arkansas Children's Nutrition Center

Title: Formula feeding and protein source alter hepatic gene expression, iron and lipid homeostasis in neonatal piglets

Authors
item Ronis, Martin -
item Chen, Ying -
item Shankar, Kartik -
item Badeaux, Jamie -
item Blackburn, Michael -
item Badger, Thomas

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: December 15, 2010
Publication Date: April 1, 2011
Citation: Ronis, M.J., Chen, Y., Shankar, K., Badeaux, J., Blackburn, M., Badger, T.M. 2011. Formula feeding and protein source alter hepatic gene expression, iron and lipid homeostasis in neonatal piglets. The FASEB Journal. 25(Meeting Abstracts):340.1.

Interpretive Summary: Although breast feeding is recommended, most US infants are formula-fed. In this study, piglets were breast-fed or were fed milk formula (MF) or soy formula (SF). This represents the closest available animal model to mimic what happens in infants. Commercial formulas were used with modifications to meet pig nutritional recommendations. Serum cholesterol was lower in piglets fed formula relative to breast-feeding and serum fats were increased in SF piglets (P<0.05). Iron levels were higher in the liver of formula-fed piglets (P<0.05). Gene array analysis revealed >2-fold changes in expression in 57 liver genes in MF vs. breast-fed and 124 liver genes in SF vs. breast-fed piglets with 44 genes in common. mRNA encoding CYP7A1, the rate limiting enzyme in conversion of cholesterol to bile acids, and hepcidin, a major regulator of iron traffic, were increased in formula-fed piglets. This explains the differences in cholesterol and iron values observed with formula feeding. In addition, SF specific increases were observed in liver CYP3A enzyme mRNA, protein and activities. In contrast, no consistent effects of SF feeding were observed on expression of 6 estrogen responsive liver genes. These data suggest formula specific effects on liver metabolism in newborns, but provide no evidence that soy infant formula has estrogenic actions in this organ.

Technical Abstract: Although breast feeding is recommended, most US infants are formula-fed. In this study, neonatal piglets were breast-fed or were fed milk formula (MF) or soy formula (SF) from PND 2 until sacrifice at PND21. Commercial formulas were used with modifications to meet pig NRC recommendations. Serum cholesterol was lower in piglets fed formula relative to breast-feeding (P<0.05) and serum triglycerides were elevated in SF piglets (P<0.05). Iron accumulation was greater in the liver of formula-fed piglets (P<0.05). Affymetrix array analysis revealed >2-fold changes in gene expression in 57 hepatic genes in MF vs. breast-fed and 124 hepatic genes in SF vs. breast-fed piglets with 44 genes in common. mRNA encoding CYP7A1, the rate limiting enzyme in conversion of cholesterol to bile acids, and hepcidin, a major regulator of hepatic iron traffic, were significantly elevated in formula-fed piglets and appear to explain the differences in cholesterol and iron homeostasis associated with formula feeding. In addition, SF specific increases were observed in hepatic CYP3A enzyme mRNA, apoprotein and activities (P<0.05). In contrast, no consistent effects of SF feeding were observed on expression of 6 estrogen responsive hepatic genes. These data suggest formula specific effects on neonatal hepatic metabolism, but provide no evidence for soy infant formula estrogenicity.

Last Modified: 8/27/2014
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