Location: Arkansas Children's Nutrition CenterTitle: Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig Author
Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2011
Publication Date: 12/1/2011
Citation: Ronis, M.J., Chen, Y., Shankar, K., Gomez-Acevedo, H., Cleves, M.A., Badeaux, J., Blackburn, M.L., Badger, T.M. 2011. Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig. Physiological Genomics. 43(23):1281-1293. Interpretive Summary: The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. A concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals – genistein and daidzein which are normally present in soy beans. We used a piglet model to look at this question. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver. We also found that overall gene expression profiles were different in male and female piglets and that feeding the formulas changed expression of some genes in a similar way and some in a unique fashion. These data suggest that soy formula does not have estrogenic effects in the infant liver and is unlikely to have adverse health effects related to estrogen-like actions.
Technical Abstract: Although the American Academy of Pediatrics recommends breast feeding for at least the first 6 months of life, formula feeding remains more popular in the US. In the current study, neonatal piglets were breast-fed or were fed commercially available milk-based formula (MF) or soy-based formula (SF) from postnatal day 2 (PND2) until sacrifice at PND21 (the usual age of weaning). Liver weights were greater in formula-fed piglets (P<0.05) than in breast-fed piglets; whereas, serum triglycerides were elevated only in SF piglets (P<0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures between piglets fed breast milk or formula, as well as between piglets fed milk formula or soy formula. For example, in males, expression of 346 hepatic genes differed between formula-fed and breast-fed piglets, and SF-fed differed from MF-fed piglets in 277 genes. Furthermore, gene expression profiles of males differed from females, even when the same diet was consumed. Serum cholesterol was lower in piglets fed formula relative to breast-fed piglets (P<0.05) and this was associated with elevations in mRNA encoding CYP7A1, the rate limiting enzyme in conversion of cholesterol to bile acids. Hepcidin, a major regulator of hepatic iron trafficking, was elevated in piglets fed formula relative to breast-fed piglets (P<-0.05) and this resulted in increased hepatic iron accumulation. Piglets fed SF had increased expression of CYP3A enzymes (P<0.05) and decreased expression of several hepatic genes involved in glucose and lipid homeostasis which have traditionally been considered estrogen-inducible. These data suggest that: 1) gene expression profiles in neonates differ significantly depending on the diet consumed which may help explain the unique beneficial health outcomes of breast milk compared with formula; 2) hepatic iron storage and cholesterol metabolism clearly differ between breast and formula feeding in piglets; 3) there is no evidence that SF is estrogenic in neonatal pig liver.