title: 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.
abstract: Stearoyl-coenzyme A desaturase 1 (SCD1) is a pivotal enzyme in the biosynthesis of monounsaturated fatty acids (MUFA). It is tightly regulated by transcription factors that control lipogenesis. In nonruminants, liver X receptor α (LXRα) is a nuclear receptor and transcription factor that acts as a key sensor of cholesterol and lipid homeostasis. However, the mechanism whereby LXRα regulates the expression and transcriptional activity of SCD1 in ruminant mammary cells remains unknown. In this study with goat mammary epithelial cells (GMEC), the LXRα agonist T 4506585 (T09) markedly enhanced the mRNA expression of SCD1 and sterol regulatory element binding factor 1 (SREBF1). The concentrations of C16:1 and C18:1 and their desaturation indices also were increased by LXRα activation. However, knockdown of LXRα did not alter the mRNA expression of SCD1. Although SCD1 was repressed by SREBF1 knockdown, T09 significantly increased SCD1 expression. Further analysis revealed that the SCD1 promoter activity was activated by LXRα overexpression. The goat SCD1 promoter contains 2 LXR response elements (LXRE), 1 sterol response element (SRE), and 1 nuclear factor Y (NF-Y) binding site. Site-directed mutagenesis of LXRE1, LXRE2, or SRE alone did not eliminate the upregulation of SCD1 when LXRα was overexpressed. In contrast, when NF-Y alone or in combination with SRE was mutated simultaneously, the basal transcriptional activity of the SCD1 promoter was markedly decreased and did not respond to LXRα overexpression. Furthermore, when SREBF1 was knocked down, overexpression of LXRα did not affect the promoter activity of SCD1. Together, these data suggest that LXRα regulates the expression of SCD1 through increasing SREBP-1 abundance to promote interaction with SRE and NF-Y binding sites. The present study provides evidence that LXRα is involved in the synthesis of MUFA in the goat mammary gland through an indirect mechanism.
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China.
authors.forename: D W
authors.initials: DW
authors.lastname: Yao
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China. Electronic address: luojun@nwsuaf.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: He
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China.
authors.forename: H F
authors.initials: HF
authors.lastname: Xu
authors.affiliation: College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, P. R. China 450046.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Animal Sciences, Zhejiang Sci-Tech University, Hangzhou, P. R. China 310058.
authors.forename: H B
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, P. R. China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801. Electronic address: jloor@illinois.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D006041:Goats / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D013230:Stearoyl-CoA Desaturase
keywords: liver X receptor α; monounsaturated fatty acids; stearoyl-CoA desaturase 1; transcriptional regulation