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Akt Serine/Threonine Kinase 1 Regulates de Novo Fatty Acid Synthesis through the Mammalian Target of Rapamycin/Sterol Regulatory Element Binding Protein 1 Axis in Dairy Goat Mammary Epithelial Cells

Author:
Zhang, Tianying, Huang, Jiangtao, Yi, Yongqing, Zhang, Xueying, Loor, Juan J., Cao, Yanhong, Shi, Huaiping, Luo, Jun
Source:
Journal of agricultural and food chemistry 2018 v.66 no.5 pp. 1197-1205
ISSN:
1520-5118
Subject:
binding proteins, dairy goats, epithelial cells, fatty acids, genes, genetic vectors, in vitro studies, lipid metabolism, mammary glands, messenger RNA, molecular cloning, phosphatidylinositol 3-kinase, phosphorylation, protein-serine-threonine kinases, rapamycin, serine, signal transduction, sterols, threonine, triacylglycerols
Abstract:
Akt serine/threonine kinase acts as a central mediator in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, regulating a series of biological processes. In lipid metabolism, Akt activation regulates a series of gene expressions, including genes related to intracellular fatty acid synthesis. However, the regulatory mechanisms of Akt in dairy goat mammary lipid metabolism have not been elaborated. In this study, the coding sequences of goat Akt1 gene were cloned and analyzed. Gene expression of Akt1 in different lactation stages was also investigated. For in vitro studies, a eukaryotic expression vector of Akt1 was constructed and transfected to goat mammary epithelial cells (GMECs), and specific inhibitors of Akt/mammalian target of rapamycin (mTOR) signaling were applied to GMECs. Results showed that Akt1 protein was highly conserved, and its mRNA was highly expressed in midlactation. In vitro studies indicated that Akt1 phosphorylation activated mTOR and subsequently enhanced sterol regulatory element binding protein 1 (SREBP1), thus increasing intracellular triacylglycerol content. Inhibition of Akt/mTOR signaling down-regulated the gene expression of lipogenic genes. Overall, Akt1 plays an important role in regulating de novo fatty acid synthesis in goat mammary epithelial cells, and this process probably is through the mTOR/SREBP1 axis.
Agid:
6042438