Milk Fat Globule Membrane Supplementation in Formula-fed Rat Pups Improves Reflex Development and May Alter Brain Lipid Composition

Sara Moukarzel,Joanne Weinberg,Bernd O Keller,Alejandra M Wiedeman,Sheila M Innis,Rajavel Elango,Cyrielle Garcia,Roger A Dyer,Guilaine Boyce

doi:10.1038/s41598-018-33603-8

Abstract

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the “pup in a cup” model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.

Highlights

Lipids in the human milk aqueous phase consist of globules formed of a triacylglycerol core surrounded by a unique membrane, the milk fat globule membrane (MFGM)[2]
The negative geotaxis reflex occurred significantly earlier in the MFGM− group compared to the mother-reared group (P = 0.015) for which the maturation age was closer to pups in the MFGM+ group (P = 0.069)
Maturation age for cliff avoidance and ear twitch reflexes were significantly different across the three groups (P < 0.001), and for both tests, the MFGM+ group was closer to the mother-reared group compared to the MFGM− group

Summary

Introduction

Lipids in the human milk aqueous phase consist of globules formed of a triacylglycerol core surrounded by a unique membrane, the milk fat globule membrane (MFGM)[2]. Interest in the biological benefits of MFGM has greatly increased over the last five years, largely driven by the recent commercial availability of bovine MFGM and its potential use as a functional dietary ingredient in infant formula. The long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) increases in the rat brain during postnatal development similar to the human and is primarily present in gray matter PE and phosphatidylserine (PS)[14,18,19,20,21]. Our objectives for the current study were to: (1) determine whether feeding MFGM improves the development of physical features and reflexes in artificially-reared rat pups; and (2) begin to elucidate potential mechanisms behind possible improved neurodevelopment with MFGM feeding

Methods

Results

Conclusion