Beyond ingredients: Supramolecular structure of lipid droplets in infant formula affects metabolic and brain function in mouse models

Abstract

Human milk beneficially affects infant growth and brain development. The supramolecular structure of lipid globules in human milk i.e., large lipid globules covered by the milk fat globule membrane, is believed to contribute to this effect, in addition to the supply of functional ingredients. Three preclinical (mouse) experiments were performed to study the effects of infant formula mimicking the supramolecular structure of human milk lipid globules on brain and metabolic health outcomes. From postnatal day 16 to 42, mouse offspring were exposed to a diet containing infant formula with large, phospholipid-coated lipid droplets (structure, STR) or infant formula with the same ingredients but lacking the unique structural properties as observed in human milk (ingredient, ING). Subsequently, in Study 1, the fatty acid composition in liver and brain membranes was measured, and expression of hippocampal molecular markers were analyzed. In Study 2 and 3 adult (Western-style diet-induced) body fat accumulation and cognitive function were evaluated. Animals exposed to STR compared to ING showed improved omega-3 fatty acid accumulation in liver and brain, and higher expression of brain myelin-associated glycoprotein. Early exposure to STR reduced fat mass accumulation in adulthood; the effect was more pronounced in animals exposed to a Western-style diet. Additionally, mice exposed to STR demonstrated better memory performance later in life. In conclusion, early life exposure to infant formula containing large, phospholipid-coated lipid droplets, that are closer to the supramolecular structure of lipid globules in human milk, positively affects adult brain and metabolic health outcomes in pre-clinical animal models.

Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age

“…It is hypothesized that differences in bioavailability of these components to the developing brain early in life may contribute to infant neurocognitive development (7). This idea is supported by a recent series of preclinical studies in mice demonstrating IF with large lipid droplets coated by PL promote n-3 LCPUFA accumulation in brain tissue and improve later in life cognitive function compared to IF with small lipid droplets and with PL present as added ingredient (21). Interestingly, the mere addition of dairy lipids and/or MFGM components to IF does not lead to structural properties of lipids similar to HM (68), nor does it appear to bring digestion and absorption kinetics closer to that of HM (69).…”

“…In preclinical experiments using mouse models, early life exposure to Concept compared to Standard IF resulted in long term improvement in metabolic health and neurocognitive outcomes ( 19 – 21 ). In a randomized, controlled trial (Dutch Trial Register; NTR3683), we demonstrated that a Concept IF with dairy lipids and comprising large lipid droplets coated by (bovine MFGM derived) PL supported adequate growth and was safe and well-tolerated in healthy term infants ( 22 ).…”