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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
Journal of Agricultural and Food Chemistry ( IF 6.1 ) Pub Date : 2018-01-25 00:00:00 , DOI: 10.1021/acs.jafc.7b05305
Tianying Zhang 1 , Jiangtao Huang 1 , Yongqing Yi 1 , Xueying Zhang 1 , Juan J. Loor 2 , Yanhong Cao 3 , Huaiping Shi 1 , Jun Luo 1
Affiliation  

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.

中文翻译:

Akt的丝氨酸/苏氨酸激酶1个调控对从头通过哺乳动物雷帕霉素靶脂肪酸合成/固醇调节元件结合蛋白1轴奶山羊乳腺上皮细胞

Akt丝氨酸/苏氨酸激酶在磷脂酰肌醇3激酶(PI3K)/ Akt信号传导途径中起着重要的调节作用,调节一系列生物学过程。在脂质代谢中,Akt激活调节一系列基因表达,包括与细胞内脂肪酸合成有关的基因。然而,Akt在奶山羊乳脂代谢中的调控机制尚未阐明。在这项研究中,山羊Akt1基因的编码序列被克隆和分析。还研究了Akt1在不同泌乳阶段的基因表达。为了进行体外研究,使用了Akt1的真核表达载体将其构建并转染至山羊乳腺上皮细胞(GMEC),并将特异的Akt /哺乳动物雷帕霉素靶标(mTOR)信号转导抑制剂应用于GMEC。结果表明,Akt1蛋白高度保守,其mRNA在泌乳期高表达。体外研究表明,Akt1磷酸化激活了mTOR,随后增强了固醇调节元件结合蛋白1(SREBP1),从而增加了细胞内三酰甘油的含量。Akt / mTOR信号转导的抑制下调了脂肪基因的基因表达。总体而言,Akt1在调节山羊乳腺上皮细胞的从头脂肪酸合成中起着重要作用,这一过程可能是通过mTOR / SREBP1轴完成的。
更新日期:2018-01-25
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