Niacin/β-hydroxybutyrate regulates milk fat and milk protein synthesis

As a crucial receptor of BHBA and niacin, GPR109A is largely expressed in the mammary gland. However, the role of GPR109A in milk synthesis and its underlying mechanism is still largely unknown. In this study, we first investigated the effect of GPR109A agonists (niacin/BHBA) on milk fat and milk protein synthesis in a mouse mammary epithelial cell line (HC11) and PMECs (porcine mammary epithelial cells). The results showed that both niacin and BHBA promote milk fat and milk protein synthesis with the activation of mTORC1 signaling. Importantly, knockdown GPR109A attenuated the niacin-induced increase of milk fat and protein synthesis and the niacin-induced activation of mTORC1 signaling. Furthermore, we found that GPR109A downstream G protein-G