Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid

Abstract

Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in the biosynthesis of palmitoleic and oleic acid. Although the transcriptional regulatory mechanism of SCD1 via polyunsaturated fatty acids (PUFA) has been extensively explored in nonruminants, the existence of such mechanism in ruminant mammary gland remains unknown. In this study, we used goat genomic DNA to clone and sequence a 1,713-bp fragment of the SCD1 5' flanking region. Deletion assays revealed a core region of the promoter located between -415 and -109 bp upstream of the transcription start site, and contained the highly conserved PUFA response region. An intact PUFA response region was required for the basal transcriptional activity of SCD1. Linoleic acid reduced endogenous expression of SCD1 and sterol regulatory element binding factor-1 (SREBF1) in goat mammary epithelial cells. Further analysis indicated that both the sterol response element (SRE) and the nuclear factor Y (NF-Y) binding site in the SCD1 promoter were responsible for the inhibition effect by linoleic acid, whereas the effect was abrogated once NF-Y was deleted. In addition, SRE and NF-Y were partly responsible for the transcriptional activation induced via the liver X receptor agonist T 4506585 (Sigma-Aldrich, St. Louis, MO). When goat mammary epithelial cells were cultured with linoleic acid, addition of T 4506585 markedly increased SCD1 transcription in controls, but had no effect on cells with a deleted SRE promoter. These results demonstrated that linoleic acid can regulate SCD1 expression at the transcriptional level through SRE and NF-Y in a liver X receptor-dependent fashion in the goat mammary gland.

Comparison of mammary lipid metabolism in dairy cows and goats fed diets supplemented with starch, plant oil, or fish oil

“…Indeed, in both species, LXRA and PPARA were significantly and negatively associated (−0.70 < r < −0.32, n = 21) with almost all the other genes, whereas significant and positive associations (+0.32 < r < +0.87, n = 22) were observed for SREBF1 and SP1, respectively, suggesting a putative implication in the repression and induction of the genes by these transcription factors, which is in line with several studies in bovines (Bionaz and Loor, 2008;Kadegowda et al, 2009;Oppi-Williams et al, 2013) and caprines (Shi et al, 2013;Xu et al, 2016;Yao et al, 2016) that reported crucial roles of these transcription factors on lipogenic gene expression. Such relationships might result from shared regulation by the same transcription factor or from concomitant regulation by different transcription factors (Harvatine and Bauman, 2006) for these genes, regulation involving microRNA (Lynn, 2009), or other mechanisms.…”

Stearoyl-CoA desaturase 1 expression is downregulated in liver and udder during E. coli mastitis through enhanced expression of repressive C/EBP factors and reduced expression of the inducer SREBP1A

“…The results obtained with vectors expressing the factor series NFY-A, -B, -C are also in line with the respective literature in that we observed in the HepG2 model for liver cells a significant stimulation (cf [ 24 ]) and slight repression in the MAC-T model for MEC, similar as recently reported using the human breast cancer line MCF7 [ 59 ]. The pivotal role of the NFY factor family for the basal and nutritional regulated activity of the SCD1 promoter has recently been underscored in goat MEC model cells [ 60 ]. We had included into this set of experiments vectors expressing the NF-κB p50 and −p65 factors not least because of the close vicinity of their cognate promoter binding site to each other and that of C/EBP factors.…”

Cadmium transcriptionally regulates Scd1 expression in silver pomfret

“…In mammals, Scd1 expression and activity are directly or indirectly regulated by a wide range of transcription factors, including Srebp1c, Lxrα, Pparγ, C/EBP‐α, NF‐1, NF‐Y, AP‐1, Sp1, thyroid hormone receptor, and peroxisome proliferator–activated receptor gamma coactivator 1‐α . Using an online database and comparing our results with a previous study, we also identified some putative Srebp1 (SRE), Pparγ, C/EBP, Lxr, NF‐Y, and Sp1 binding sites. A luciferase assay showed that overexpression of Srebp1 and Pparγ produced a 2‐fold increase in the activity of the scd1 promoter.…”

“…These results indicated that Cd might regulate the expression of scd1 through Srebp1. Similarly, this mechanism is responsible for polyunsaturated fatty acids/cholesterol‐mediated scd1 expression in mammals . In mammals, Srebp1 has been indicated to regulate the expression of Scd1 through an SRE in its promoter region .…”