Lipidome Analysis in Brain and Peripheral Plasma Following Milk Fat Globule Membrane Supplementation in Rodents

Scope Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigates bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induces parallel changes to plasma and brain lipidomes. Methods and results Transgenic APOE*3.Leiden mice (n = 18 per group) and Sprague–Dawley rats (n = 12 per group) are fed bMFGM‐enriched (MFGM+) or Control diet, followed by phospholipid profile‐determination in plasma, hippocampus, and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrates a separation between MFGM+ and Control plasma across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) are consistently higher in the circulation of MFGM+ groups. A similar trend is observed in rat prefrontal cortex, although no significant separation of the brain lipidome is demonstrated. Conclusion bMFGM‐enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with similar, but non‐significant, trends in central brain regions. These changes may contribute to the beneficial effects of bMFGM on neurodevelopment during early life. Milk fat globule membrane (MFGM) is a complex component of milk contributing to infant neurodevelopment. This study investigates the bioavailability of lipids in blood and brain of rodents feed MFGM‐enriched diets, analyzed by mass spectrometry. A clear difference is observed in lipid profiles from blood when fed MFGM‐enriched versus Control diets, with similar patterns in the brain. These changes may contribute to the beneficial effects of dietary MFGM on cognitive development in early life.