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硬脂酸通过 FATP4-CDK1 激活 PI3K-mTOR-4EBP1/S6K 和 mTOR-SREBP-1 信号通路促进原代奶牛乳腺上皮细胞的乳合成。

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.

机构信息

College of Veterinary Medicine, Jilin University, Changchun 130062, China.

出版信息

J Agric Food Chem. 2022 Apr 6;70(13):4007-4018. doi: 10.1021/acs.jafc.2c00208. Epub 2022 Mar 25.

DOI:10.1021/acs.jafc.2c00208
PMID:35333520
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 3 (3.713 ± 0.583) and 4 (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.

摘要

硬脂酸(SA)是一种 18 个碳长链饱和脂肪酸,具有促进泌乳的巨大潜力。因此,本研究探讨了 SA 对原代奶牛乳腺上皮细胞(BMECs)中乳汁合成的影响及其作用机制。在本研究中,我们发现 SA 可显著增加β-酪蛋白和甘油三酯的含量,在 100μM 时效果最为显著。信号通路研究发现,SA 通过上调细胞周期蛋白依赖性激酶 1(CDK1)激活 PI3K-mTOR-4EBP1/S6K 和 mTOR-SREBP-1 通路来影响乳汁合成。此外,当用 SA 处理 BMECs 时,我们检测到脂肪酸转运蛋白(FATPs);在 100μM 时,3(3.713±0.583)和 4(40.815±8.959)的 mRNA 水平显著上调。随后,我们构建了 FATP4-siRNA,并发现 SA 通过 FATP4 进入 BMECs 进行转运,从而促进乳汁合成。综上所述,这些结果表明,SA 通过 FATP4-CDK1 激活 PI3K-mTOR-4EBP1/S6K 和 mTOR-SREBP-1 信号轴来促进 BMECs 中的乳汁合成。

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