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

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.