Kisspeptin-10 Maintains the Activation of the mTOR Signaling Pathway by Inhibiting SIRT6 to Promote the Synthesis of Milk in Bovine Mammary Epithelial Cells.

Kisspeptin-10 (Kp-10) is a peptide hormone that regulates normal physiological processes. The mechanism of Kp-10 in milk synthesis is still unclear. Therefore, bovine mammary epithelial cells (BMECs) were used to study the mechanism by which Kp-10 affects milk synthesis in BMECs. The GPR54 inhibitor and SIRT6 overexpression plasmid and siRNA were used to study the mechanism of regulating milk protein and milk fat synthesis by Kp-10. The results showed that 100 nM Kp-10 increased milk synthesis in BMECs. SIRT6 overexpression could significantly reduce the milk protein and milk fat synthesis in BMECs. Moreover, overexpression of SIRT6 reversed the activation of the Kp-10-induced mTOR signaling pathway. Further analysis suggested that SIRT6 might regulate the signal transduction of mTOR at the transcriptional level. These results strongly suggested that Kp-10/GPR54 activated the mTOR signaling pathway by inhibiting SIRT6 expression and then increased the milk synthesis in BMECs.