Liver <scp>X</scp> receptor activation increases hepatic fatty acid desaturation by the induction of <scp>SCD1</scp> expression through an <scp>LXR</scp>α‐<scp>SREBP1c</scp>‐dependent mechanism (肝X受体活化可通过LXRα‐SREBP1c依赖的机制诱导SCD1表达来增加肝脏脂肪酸不饱和度)

Zhang, Xiaoyan; Liu, Jia; Su, Wen; Wu, Jing; Wang, Chunjiong; Kong, Xiaomu; Gustafsson, Jan Åke; Ding, Jie; Ma, Xiaosong; Guan, Youfei

doi:10.1111/1753-0407.12081

Cited by 38 publications

(35 citation statements)

References 26 publications

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“…31 In fact, a synthetic nonsteroidal LXR agonist, T0901317, strongly increases protein and mRNA expressions of SCD1 and SREBP-1. These data are in agreement with a previous study, 47 where SCD1 upregulation induced by T0901317 resulted mainly through a SREBP-1 increase. In addition, SREBP-1 expression completely abolished T0901317mediated SCD1 induction.…”

Section: Discussionsupporting

confidence: 94%

“…These data are in agreement with a previous study, where SCD1 upregulation induced by T0901317 resulted mainly through a SREBP‐1 increase. In addition, SREBP‐1 expression completely abolished T0901317‐mediated SCD1 induction . SREBP‐1 could be regulated at transcriptional level by a direct LXR binding to specific promoter sequences …”

Section: Discussionsupporting

confidence: 93%

“…Therefore, in this study, we focused our attention on a possible direct LXR regulation by PUFAs, and in particular, we considered the alpha isoform, the most highly expressed in liver and most abundant in tissues involved in lipid metabolism . In addition, previous evidences showed that LXR α but not LXR β is required for TO901317‐induced SCD1 regulation in the liver . SPR results showed significant K D values for DHA, EPA and AA, equal to 119.0 ± 17.1, 155.0 ± 36.2 and 15.5 ± 3.4 nM, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP‐1 interaction with a specific SCD1 promoter element

Caputo

Rosa

Rescigno

et al. 2014

Cell Biochemistry & Function

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Stearoyl-CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element-binding protein-1 (SREBP-1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP-1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP-1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP-1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP-1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP‐1 interaction with a specific SCD1 promoter element

Caputo

Rosa

Rescigno

et al. 2014

Cell Biochemistry & Function

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“…SCD1 expression is regulated by diverse hormonal and nutritional factors [15–18]. It is positively regulated by SREBP-1c, CHREBP, and LXR which could explain the induction of SCD1 expression during fasting-refeeding cycles [2, 19]. …”

Section: Stearoyl Coa Desaturase (Scd)mentioning

confidence: 99%

Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism

Aljohani

Syed

Ntambi

2017

Trends in Endocrinology & Metabolism

203

133

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Stearoyl CoA desaturase 1 (SCD1) is a central regulator of fuel metabolism and may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets. In this review, we evaluate the role of SCD1 isoform in regulation of lipid and glucose metabolism in metabolic tissues. These highlights of recent findings are aimed towards advancing our understanding of the role of SCD1 in the development of metabolic diseases which may help evaluate the possible health outcomes of modulating MUFA levels through targeting SCD1 activity.

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“…Currently, platelet reactivity, lipid infiltration, and vascular endothelial cell injury are thought to be the main pathological processes involved in ischemic stroke (Jansen et al, 2013;Orozco et al, 2013). Similarly to ischemic heart disease, lipid metabolism disorder is an independent risk factor for stroke (Jakobsson et al, 2012;Zhang et al, 2013). Liver X receptor a (LXRa) is a class of nuclear receptor family members (Sharma et al 2013) that are mainly distributed in the liver, adipose tissue, kidney, small intestine, and macrophages and control the stable internal environment of cholesterol level, lipoprotein metabolism, and fat synthesis (A-González and Castrillo, 2011).…”

Section: Introducitonmentioning

confidence: 99%

Association of liver X receptor α (LXRα) gene polymorphism and ischemic stroke

et al. 2015

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ABSTRACT. We examined the relationship between the liver X receptor a gene (LXRα) rsl2221497 polymorphism and the susceptibility to ischemic stroke in a Chinese population. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect the genotype of rsl2221497 in the LXRα gene of 300 stroke patients and 300 healthy control subjects. The chi-square test was used to analyze the genotype distribution between the 2 groups. We found that the risk of stroke in carriers with the AA + GA genotype was 2.12-fold higher than that in GG genotype carriers (odds ratio = 2.12, 95% confidence interval: 1.58-2.99, P < 0.05). The risk of stroke in carriers of the A allele increased by 1.03-fold compared to that in G allele carriers (odds ratio = 2.03, 95% confidence interval: 1.44-3.01, P < 0.01). After adjusting for other confounding factors such smoking, hypertension, and diabetes, the A allele was found to be an independent risk factor for stroke. Therefore, the rsl2221497 polymorphism in the LXRα gene

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Liver X receptor activation increases hepatic fatty acid desaturation by the induction of SCD1 expression through an LXRα‐SREBP1c‐dependent mechanism (肝X受体活化可通过LXRα‐SREBP1c依赖的机制诱导SCD1表达来增加肝脏脂肪酸不饱和度)

Abstract: Taken together, the present studies demonstrate that pan-LXR activation increases hepatic fatty acid desaturation via the induction of SCD1 expression in an LXRα-dependent and SREBP1c-mediated manner.

Cited by 38 publications

References 26 publications

Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP‐1 interaction with a specific SCD1 promoter element

Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP‐1 interaction with a specific SCD1 promoter element

Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism

Association of liver X receptor α (LXRα) gene polymorphism and ischemic stroke

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