Lactosomes: Structural and Compositional Classification of Unique Nanometer-Sized Protein Lipid Particles of Human Milk

Abstract

Milk fat globules (MFG) are accepted primarily as triacylglycerol delivery systems. The identification of nanometer-sized lipid-protein particles termed ‘lactosomes’ that do not contain triacylglycerol raises the question of their possible functions. MFGs were isolated by slow centrifugation and lactosomes were isolated by ultracentrifugation at a density equivalent to plasma HDL (d > 1.063 g/ml) from human milk obtained from six volunteers at different lactation stages. Isolated lactosomes were analyzed and compared with MFGs for their size distribution, lipidome, proteome, and functional activity. Lactosomes from early milk—day 8, were found to be similar in size as those from mature milk >28 days averaging ~25 nm in diameter. In total, 97 non-redundant proteins were identified in the MFG and lactosome fractions, 46 of which were unique to the MFG fraction and 29 of which were unique to the lactosome fraction. The proteins identified in the lactosome and MFG fractions were enriched with proteins identified with immunomodulatory pathways. Unlike MFGs and GM1 laden reconstituted high- density lipoprotein (rHDL) that served as a positive control, lactosomal binding capacity to cholera toxin was weak. Lipidomic analyses found that lactosomes were devoid of triacylglycerol and gangliosides, unlike MFGs, but rich in a variety of phospholipid species. The data found differences in structure, composition and function between lactosomes and MFG suggesting these two particles are derived from different biosynthetic and/or secretory pathways. The results reveal a bioactive lipid-protein, nanometer-length scale particle that is secreted into milk not to supply energy to the infant, but to play unique, protective and regulatory roles.

A novel infant milk formula concept: Mimicking the human milk fat globule structure

“…Membrane vesicles in milk have been identified as "lactosomes", "exosomes" and "lipoprotein particles" [36,37]. Several types of membranes and organelles of the mammary secretory cells have been observed in cytoplasmic crescents, including secretory vesicles containing the components of the aqueous phase of milk and ribosome-studded vesicles from the endoplasmic reticulum [38].…”

Structure–function relationship of the milk fat globule

“…The smallest MFGs (<1 mm, 80% of total by number) develop a very large lipid interface surface, which is the key parameter in determining the susceptibility of MFGM to digestive hydrolysis and reactivity [12]. Similarly, in human milk, the question of the precise regulatory and protective role played by nanometersized lipid-protein particles termed 'lactosomes' [15] is still open. The difference in metabolic fate of this fraction when ingested by neonates or adults remains to be elucidated, specifically when put in the light of the study indicating that the structure of dietary fat, among which droplet size, plays a key role in nutritional programming [13,14 && ].…”

The relationship between size and lipid composition of the bovine milk fat globule is modulated by lactation stage

“…Polar and neutral lipids were identified and quantified by HPLC (HP 1200, Agilent) combined with an evaporative light-scattering detector (ELSD, Agilent) according to a previously described protocol for normal-phase lipid separation (Argov-Argaman et al, 2010). The separation process was managed by ChemStation software for data acquisition from the ELSD.…”