Liver X receptor α promotes the synthesis of monounsaturated fatty acids in goat mammary epithelial cells via the control of stearoyl-coenzyme A desaturase 1 in an SREBP-1-dependent manner

摘要

Stearoyl-coenzyme A desturase 1 (SCD1) is is tightly regulated by transcription factors thatrncontrol lipogenesis. In non-ruminants, liver X receptor α (LXRα) is a nuclear receptor andrntranscription factor that acts as a key sensor of cholesterol and lipid homeostasis. However,rnthe mechanism whereby LXRα regulates the expression and transcriptional activity of SCD1rnin ruminant mammary cells is still unknown. In this study with goat mammary epithelial cellsrn(GMEC), the LXRα agonist T0901317 (T09) enhanced markedly the mRNA expression ofrnSCD1 and sterol regulatory element binding factor 1 (SREBF1). The concentration of C16:1rnand C18:1 and their desaturation indices also were increased by LXRα activation. However,rnknockdown of LXRα did not alter the mRNA expression of SCD1. Although SCD1 wasrnrepressed by SREBF1 knockdown, T09 significantly increased SCD1 expression. Furtherrnanalysis revealed that the SCD1 promoter activity was activated by LXRα overexpression. Therngoat SCD1 promoter contains two LXR response elements (LXRE), one sterol responsernelement (SRE) and one nuclear factor Y (NF-Y) binding site. Site-directed mutagenesis ofrnLXRE1, LXRE2 or SRE alone did not eliminate the upregulation of SCD1 when LXRα wasrnoverexpressed. In contrast, when NF-Y alone or in combination with SRE was mutatedrnsimultaneously, the basal transcriptional activity of the SCD1 promoter was markedlyrndecreased and did not respond to LXRα overexpression. Furthermore, when SREBF1 wasrnknocked down, overexpression of LXRα did not affect the promoter activity of SCD1.rnTogether, these data suggested that LXRα regulates the expression of SCD1 throughrnincreasing SREBP-1 abundance to promote interaction with the SRE and NF-Y binding sites.rnThe present study provides evidence that LXRα is involved in the synthesis of MUFA in therngoat mammary gland through an indirect mechanism.