Author
BABAWALE, ELIZABETH - University Of Manitoba | |
JONES, PETER JH - University Of Manitoba | |
MERCER, KELLY - University Arkansas For Medical Sciences (UAMS) | |
LIN, HAIXIA - University Arkansas For Medical Sciences (UAMS) | |
YERUVA, LAXMI - University Arkansas For Medical Sciences (UAMS) | |
BAR YOSEPH, FABIANA - Enzymotec Ltd | |
RUTHERFORD, SHANE - Massey University |
Submitted to: Nutrients
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/21/2018 Publication Date: 12/1/2018 Citation: Babawale, E.A., Jones, P., Mercer, K.E., Lin, H., Yeruva, L., Bar Yoseph, F., Rutherford, S.M. 2018. Modulating sterol concentrations in infant formula influences cholesterol absorption and synthesis in the neonatal piglet. Nutrients. 10(12):1848. https://doi.org/10.3390/nu10121848. DOI: https://doi.org/10.3390/nu10121848 Interpretive Summary: Most commercially available infant formulas are made with vegetable oils. These oils contain plant-based lipids called phytosterols (PS), which are structurally similar to cholesterol. Dietary cholesterol uptake during formula feeding is low compared to those infants fed breast milk. One possible reason for lower cholesterol absorption with formula feeding is that PS compete with cholesterol for the uptake via the cholesterol transporter, Npc1l1, present in the intestine. In the formula-fed infant, the liver may increase synthesis of cholesterol as a compensatory mechanism for the low dietary uptake. To test this idea, we fed groups of piglets (7 days old) different infant formulas containing high or low concentrations of PS and/or cholesterol for 3 wks. Increased cholesterol absorption was associated with a decrease in markers of hepatic cholesterol synthesis. These results suggest that reducing PS concentrations in infant formula may improve dietary cholesterol absorption in formula-fed infants. Technical Abstract: Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research. |