Lysine Enhances the Stimulation of Fatty Acids on Milk Fat Synthesis via the GPRC6A-PI3K-FABP5 Signaling in Bovine Mammary Epithelial Cells

Amino acids can enhance milk fat synthesis in bovine mammary epithelial cells (BMECs), but the molecular mechanism is not well-known. In this study, we explored the regulatory role and molecular mechanism of lysine (Lys) on milk fat synthesis induced by fatty acids (FAs). We show that Lys dose-dependently affects number of cells and milk fat synthesis, and has more stimulatory effects in the presence of FAs. Lys enhances FA-induced sterol regulatory element binding protein 1c (SREBP-1c) expression and maturation in a fatty-acid-binding protein 5 (FABP5)-dependent manner. We further show that the Lys stimulates FABP5 expression via the GPRC6A (GPCR, class C, group 6, subtype A)-PI3K (phosphatidylinositol 3-kinase) signaling. Lys dose-dependently affects GPRC6A expression and localization at the plasma membrane. In summary, our data reveals that Lys enhances FAs-stimulated SREBP-1c expression and maturation leading to milk fat synthesis via the GPRC6A-PI3K-FABP5 signaling in BMECs.