Comparative Proteomic Analysis of Paired Human Milk Fat Globules and Membranes and Mouse Milk Fat Globules Identifies Core Cellular Systems Contributing to Mammary Lipid Trafficking and Secretion

Abstract

Human milk delivers critical nutritional and immunological support to the infant. The milk fat globule and its membrane contain many bioactive components, yet the mechanism of milk fat secretion and how milk fat globule (MFG) components are regulated are poorly defined. In this study, we perform quantitative proteomic profiling of milk fat globules from human and mouse milk, as well as from isolated membranes physically disrupted from human milk fat globules.Using paired analyses of the human samples we report membrane enrichment of the proteins involved in docking/tethering the lipid droplet to the membrane as well as minor components involved in the signaling pathway for secretion. Comparing abundance between human and mouse milk fat globules we find that 8 of 12 major milk fat globule proteins are shared between the two species. Comparative pathway enrichment analyses between human and mouse samples reveal similarities in shared membrane trafficking and signaling pathways involved in milk fat secretion. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse milk fat globules in greater detail, provide a quantitative profile of specifically enriched human milk fat globule membrane proteins, and identify core cellular systems involved in milk lipid secretion.

Milk Fat Globules: 2024 Updates

“…158 Many proteomic studies have listed several casein and whey proteins in the MFG membrane. 159 Casein digestion may produce several bioactive peptides, which have been linked to gastrointestinal and immunological function, neurodevelopment, and even the effectiveness of antibiotics and probiotics. 160 Lactoferrin, a whey protein, is detectable both bound to the MFGM and in the aqueous phase of milk.…”

Milk lipid and milk fat globule membrane production

“…Lipid travels to the apical surface of the mammary epithelial cell and is then enveloped by the plasma membrane and released as an MFG in 'an apocrine mechanism which is incompletely understood' (Martin Carli et al 2023).…”