Kinetics of milk lipid droplet transport, growth, and secretion revealed by intravital imaging: lipid droplet release is intermittently stimulated by oxytocin

Abstract

Intravital imaging reveals how lipid droplets are assembled and secreted into milk from mammary epithelial cells. Lipid droplets grow by fusing with each other during transport to the surface, in nucleation centers in the cell apex and even during secretion. Oxytocin plays a major role in the expulsion of droplets still associated with the cell.

Physiology of milk secretion

“…3D). Recently, the final expulsion of MFGs has been shown to occur after OT-mediated contraction of the myoepithelial cells [60]. This observation is compatible with the above scenario and suggest that milk secretion processes are spatiotemporally coupled and regulated by both hormonal and mechanical factors.…”

“…The MFG is a major energy source for the newborn and also contains numerous enzymes, immunomodulatory factors, such as lactadherin/MFG-E8 and BTN1. Lipid secretion is regulated by hormones such as PRL [59] and OT through mechanical deformation of MECs upon myoepithelial cells contraction [60].…”

“…As OT receptors are also present in MECs [66], this hormone may also exert direct effects on the secretory activity of MECs (Fig. 3D) [50,60]. Milk is then expelled out of the alveoli into the ducts and lactiferous sinuses.…”

Lipid droplet functions beyond energy storage

“…For example, in the cells of the mammary epithelium, LDs originate from basally located ER and then move to apical regions, often growing and fusing during this process [204]; the apical LDs are then secreted and give rise to the fat globules present in milk. An analogous situation occurs during insect oogenesis where LDs produced in nurse cells, the sister cells of the oocyte, are moved, via cytoplasmic bridges, to the oocyte and ultimately serve as an energy supply for the developing embryo [154].…”

Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

“…For example, IVM of lipid droplets in epithelial cells of a surgically exposed lactating mammary gland highlighted the fate of lipid droplets from their synthesis in the endoplasmic reticulum to secretion at the apical plasma membrane in a live mouse ( Fig. 1A; Masedunskas et al, 2017). Furthermore, IVM in surgically exposed tissues was used to characterise the role of the actomyosin cytoskeleton during exocytosis in the salivary gland (Milberg et al, 2017), to probe secretion and paracellular transport in the liver (Porat-Shliom et al, 2016) and to visualise T-and B-cell interactions in the germinal centre of intact lymph nodes (Xu et al, 2013a).…”