Glycitin Targets the Orphan Receptor GPR3 to Promote Milk Fat Synthesis in Goat Mammary Epithelial Cells

Abstract

Milk fat is a major determinant of dairy product quality, but the receptor mechanisms by which dietary isoflavones regulate mammary lipid metabolism remain unclear. We examined glycitin-induced lipid synthesis in goat mammary epithelial cells (GMECs) and the involvement of G protein-coupled receptor 3 (GPR3). Glycitin increased triglyceride accumulation, lipid droplet formation, and lipogenic gene expression. Docking and molecular dynamics suggested a plausible glycitin–GPR3 interaction, while the increase in cyclic adenosine monophosphate (cAMP) was weakened by GPR3 knockdown. Glycitin also increased GPR3 expression and reduced MYC-associated factor X (MAX)-associated transcriptional repression. GPR3 knockdown reduced triglycerides, diacylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs). These findings identify GPR3-associated signaling as a potential mechanism linking glycitin to enhanced milk fat synthesis in GMECs.