Different roles of liver X receptor α and β in lipid metabolism: Effects of an α-selective and a dual agonist in mice deficient in each subtype

Lund, Erik; Peterson, Laurence B.; Adams, Alan D.; Lam, My-Hanh; Burton, Charlotte; Chin, Jayne; Guo, Qiu; Huang, Shaei; Latham, Melanie; Lopez, Jacqueline C.; Menke, John; Milot, Denise P.; Mitnaul, Lyndon J.; Rex-Rabe, Sandra; Rosa, Raymond; Tian, Jenny; Wright, Samuel D.; Sparrow, Carl P.

doi:10.1016/j.bcp.2005.11.004

Cited by 135 publications

(119 citation statements)

References 44 publications

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“…Most of them are dual agonists, activating both LXRα and LXRβ, and present both the favourable effects on cholesterol metabolism and the unfavourable effects on fatty acid metabolism. Treating mice deficient in either LXRα, LXRβ or both, with an agonist displaying equal potency for both isoforms or an agonist selective for LXRα, demonstrated that specific activation of LXRα or LXRβ yields distinctive lipid outcomes in vivo [74]. Most importantly, this study lends further support to the hypothesis that a specific agonist of LXRβ would raise plasma HDL-cholesterol levels and increase the expression of ABCA1 in macrophages (stimulating therefore cholesterol efflux), without causing liver triglyceride accumulation.…”

Section: Page 14 Of 35supporting

confidence: 58%

Liver X receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis

Fiévet¹,

Staels²

2009

Biochemical Pharmacology

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To cite this version:C. Fiévet, B. Staels. Liver X Receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis. Biochemical Pharmacology, Elsevier, 2009, 77 (8) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 AbstractLiver X Receptors (LXRs) are nuclear receptors that play a crucial role in regulating the expression of genes involved in lipid metabolism. Ligand activation of LXRs improves cholesterol homeostasis via multiple coordinated effects, and this function is likely to explain in part the protective effects of LXR activation on atherosclerosis reported in animal models. However, LXR activation may also induce undesirable side effects, such as lipogenesis and hypertriglyceridemia. This review discusses the potential to develop LXR modulators as therapeutic agents for atherosclerosis.

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Section: Page 14 Of 35supporting

confidence: 58%

Liver X receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis

Fiévet¹,

Staels²

2009

Biochemical Pharmacology

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“…Kotokorpi et al [52] found that one LXR endogenous ligand, GW3965, is able to reduce the secretion of bile acids and increase lipid storage. Other synthetic agonists, including T0901317 and N,N-dimethyl-3b-hydroxycholenamide, have also been used to identify the functions of NR1H3 [53]. In such circumstances, since NR1H3 is involved in hepatic development, it is possible that the addition of NR1H3 agonists to the HepaRG culture medium might be an alternative approach to accelerate HepaRG cell hepatocyte differentiation in vitro.…”

Section: Discussionmentioning

confidence: 99%

Liver X receptor α (LXRα/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4α

Chen

Pernelle

Tsai³

et al. 2014

Journal of Hepatology

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“…5 To support this, it has been shown that NR1H3 agonists raise plasma HDLcholesterol and triglyceride levels. 22 Therefore, NR1H3 plays a central role in many pathways involved in the onset of the metabolic syndrome, especially in HDL-cholesterol metabolism. It is worth noting that no significant association could NR1H3 polymorphisms and metabolic syndrome V Legry et al be detected between NR1H3 SNPs and plasma triglyceride concentrations in our study.…”

Section: Discussionmentioning

confidence: 99%

Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations

et al. 2008

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Context:The metabolic syndrome is a complex and multifactorial disorder often associated with type 2 diabetes mellitus and cardiovascular diseases. The liver X receptor a (NR1H3) plays numerous roles in metabolic pathways involved in metabolic syndrome. Objective: In the search for susceptibility genes to metabolic syndrome, we hypothesized that common genetic variation in NR1H3 gene influences metabolic syndrome susceptibility. Design: Two large French population-based studies (n ¼ 1130 and 1160) including overall 664 individuals with and 1626 individuals without metabolic syndrome were genotyped for three polymorphisms (rs12221497, rs11039155 and rs2279239) of NR1H3. Results: We found that the À6A allele of rs11039155 was consistently associated with a 30% reduction in risk of metabolic syndrome in the two independent population samples (adjusted OR (95% CI) ¼ 0.68 (0.53-0.86), P ¼ 0.001 for the combined sample). Moreover, it was associated with an increase in plasma HDL-cholesterol concentrations (P ¼ 0.02 for the combined sample). Neither rs12221497 nor rs11039155, both polymorphisms located in the 5 0 region of NR1H3, had significant influence on NR1H3 and ATP-binding cassette transporter A1 (ABCA1) gene expression in primary human macrophages. Conclusions: These results suggest that NR1H3 plays an important role in the HDL-cholesterol metabolism and in the genetic susceptibility to metabolic syndrome.

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Different roles of liver X receptor α and β in lipid metabolism: Effects of an α-selective and a dual agonist in mice deficient in each subtype

Cited by 135 publications

References 44 publications

Liver X receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis

Liver X receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis

Liver X receptor α (LXRα/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4α

Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations

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