Milk fat globule size: Unraveling the intricate relationship between metabolism, homeostasis, and stress signaling

Fat is an important component of milk which delivers energy, nutrients, and bioactive molecules from the lactating mother to the suckling neonate. Milk fat consists of a complex mixture of different types of lipids; hundreds of fatty acids, triglycerides, phospholipids, sphingolipids, cholesterol and cholesteryl ester, and glycoconjugates, secreted by the mammary gland epithelial cells (MEC) in the form of a lipid-protein assembly termed the milk fat globule (MFG). The mammary gland in general, and specifically that of modern dairy cows, faces metabolic stress once lactation commences, which changes the lipogenic capacity of MECs directly by reducing available energy and reducing factors required for both lipid synthesis and secretion or indirectly by activating a proinflammatory response. Both processes have the capacity to change the morphometric features (e.g., number and size) of the secreted MFG and its precursor-the intracellular lipid droplet (LD). The MFG size is tightly associated with its lipidome and proteome and also affects the bioavailability of milk fat and protein. Thus, MFG size has the potential to regulate the bioactivity of milk and dairy products. MFG size also plays a central role in the functional properties of milk and dairy products such as texture and stability. To understand how stress affects the structure-function of the MFG, we cover: (i) The mechanism of production and secretion of the MFG and the implications of MFG size, (ii) How the response mechanisms to stress can change the morphometric features of MFGs, and (iii) The possible consequences of such modifications.