Stearic Acid Activates the PI3K-mTOR-4EBP1/S6K and mTOR-SREBP-1 Signaling Axes through FATP4-CDK1 To Promote Milk Synthesis in Primary Bovine Mammary Epithelial Cells
Feng Li, Guiqiu Hu, Xiaoyu Long, Yu Cao, Qianqian Li, Wenjin Guo, Jiaxin Wang, Juxiong Liu, Shoupeng Fu
Abstract
Stearic acid (SA), an 18-carbon long-chain saturated fatty acid, has great potential for promoting lactation. Therefore, this study investigates the effects and mechanism of SA on milk synthesis in primary bovine mammary epithelial cells (BMECs). In our study, we found that SA significantly increased β-casein and triglycerides, and the effect was most significant at 100 μM. Signaling pathway studies have found that SA affects milk synthesis by upregulating cyclin-dependent kinase 1 (CDK1) to activate PI3K-mTOR-4EBP1/S6K and mTOR-SREBP-1 pathways. Furthermore, we detected fatty acid transport proteins (FATPs) when BMECs were treated with SA; the mRNA levels of FATP3 (3.713 ± 0.583) and FATP4 (40.815 ± 8.959) were significantly upregulated at 100 μM. Subsequently, we constructed FATP4-siRNA and found that SA was transported by FATP4 into BMECs, promoting milk synthesis. Collectively, these results revealed that SA activated PI3K-mTOR-4EBP1/S6K and mTOR-SREBP-1 signaling axes through FATP4-CDK1 to promote milk synthesis in BMECs.