Modulating Sterol Concentrations in Infant Formula Influences Cholesterol Absorption and Synthesis in the Neonatal Piglet.

Elizabeth Babawale,Laxmi Yeruva,Peter Jones,Haixia Lin,Shane Rutherfurd,Kelly Mercer,Fabiana Bar Yoseph

doi:10.3390/nu10121848

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.

Highlights

Cholesterol is essential for life, especially during the rapid growth of infants, as it is a structural element of the cell membrane lipid layer; a substrate for the production of steroid hormones, vitaminD, and bile acids [1]; crucial for proper brain development and myelin formation; and plays a key role in lipoprotein synthesis and metabolism [2]
Given that plasma cholesterol concentrations are determined by the balance between dietary sterol absorption from the gastrointestinal tract and whole body endogenous cholesterol synthesis [18], it is possible that circulating PS concentrations during infancy could be important for proper lipid programming and metabolism in later life [19]
2018, 10,2018, 184810, x FOR PEER REVIEW. These findings suggest that hepatic cholesterol synthesis is reduced in piglets fed low PS formula. These findings suggest that hepatic cholesterol synthesis is reduced in piglets fed low PS formula supplemented with cholesterol, relative to the other diet groups

Summary

Introduction

Cholesterol is essential for life, especially during the rapid growth of infants, as it is a structural element of the cell membrane lipid layer; a substrate for the production of steroid hormones, vitaminD, and bile acids [1]; crucial for proper brain development and myelin formation; and plays a key role in lipoprotein synthesis and metabolism [2]. Nutrients 2018, 10, 1848; doi:10.3390/nu10121848 www.mdpi.com/journal/nutrients (15–50 mg/L), which originates mainly from dairy milk fat [2,7]. This difference in cholesterol content results in about a three to five times higher intake of cholesterol in breast-fed infants compared to formula-fed infants [2,8]. Given that plasma cholesterol concentrations are determined by the balance between dietary sterol absorption from the gastrointestinal tract and whole body endogenous cholesterol synthesis [18], it is possible that circulating PS concentrations during infancy could be important for proper lipid programming and metabolism in later life [19]. The long-term effects of consuming diets relatively high in PS during infancy are yet to be explored [6]

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