Activation of liver X receptor promotes fatty acid synthesis in goat mammary epithelial cells via modulation of SREBP1 expression

Abstract

In bovine mammary tissue and cells, liver X receptor (LXR) regulates lipid synthesis mainly via transactivation of the transcription factor sterol regulatory element binding protein 1 (SREBP1). In the present work, we investigated the role of LXR in controlling lipid synthesis via transactivation of SREBP1 in goat primary mammary cells (GMEC). The GMEC were treated with a synthetic agonist of LXR, T0901317, and transactivation and transcription of SREBP1, expression of lipogenic genes, and fatty acid profiling and triacylglycerol (TAG) content of the cells were measured. A mild increase in the mRNA expression level of LXRα (NR1H3) was observed following treatment with different concentrations of T0901317, and a dose-dependent increase in mRNA and transactivation of SREBP1 was detected. Activation of LXR resulted in a significant increase in the mRNA expression of most of the measured genes related to de novo synthesis, desaturation, and transport of fatty acids; TAG synthesis; and transcription regulators. Compared with the control, total content of cellular TAG increased by more than 20% with T0901317 treatment. Furthermore, addition of T0901317 increased the proportion of unsaturated fatty acids (e.g., C16:1, C18:1, C20:1, and C22:1), and decreased the proportion of saturated fatty acids (e.g., C16:0, C18:0, C20:0, and C22:0). These results provide evidence that LXR regulates the expression and activity of SREBP1. Our results indicated that LXR participate in regulating the transcription of genes involved in milk fat synthesis in GMEC in an SREBP1-dependent fashion.

Keywords: SREBP1; lactation; lipid synthesis; liver X receptor; milk fat.