Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

Abstract Background Kp-10 is a peptide hormone mainly involved in the initiation tissue development in puberty. Recent studies have shown that Kp-10 is involved in fat synthesis. However, the role of Kp-10 in milk fat synthesis in lactating dairy cows has not been reported. Therefore, this study investigated the correlation between GPR54 and milk fat synthesis in dairy cows and to study the underlying mechanism in BMECs. Results The results showed that the expression of GPR54, SREBP1 and FASN in mammary glands of high-milk fat dairy cows were significantly higher than those in mammary glands of low-milk fat dairy cows. Meanwhile, 10nM Kp-10 can significantly inhibit AMPK/SIRT6 signaling pathway and promote milk fat synthesis in BMECs through its receptor GPR54. Overexpression of SIRT6 significantly reduced the acetylation level of SREBP1 and milk fat synthesis in BMECs.Conclusions These results suggested that Kp-10 inhibits the AMPK / SIRT6 signaling pathway by mediating GPR54, thereby increasing SREBP1 acetylation levels and increasing milk fat synthesis in BMECs.