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

J Agric Food Chem. 2018 Feb 7;66(5):1197-1205. doi: 10.1021/acs.jafc.7b05305. Epub 2018 Jan 25.

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.

Keywords: Akt1; goat; lipid; mammary.

MeSH terms

  • Animals
  • Epithelium / metabolism
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation / physiology
  • Goats*
  • Lipogenesis / genetics
  • Mammary Glands, Animal / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / physiology*
  • Signal Transduction / physiology
  • Sterol Regulatory Element Binding Protein 1 / physiology*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Fatty Acids
  • Sterol Regulatory Element Binding Protein 1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases