Liver X receptors in lipid metabolism: opportunities for drug discovery

2014 ◽  
Vol 13 (6) ◽  
pp. 433-444 ◽  
Author(s):  
Cynthia Hong ◽  
Peter Tontonoz
Keyword(s):  
Lipid Metabolism ◽  
Drug Discovery ◽  
Liver X Receptors ◽  
X Receptors

scholarly journals Liver X Receptors and Male (In)fertility

2019 ◽  
Vol 20 (21) ◽  
pp. 5379 ◽  
Author(s):  
Sheba Jarvis ◽  
Catherine Williamson ◽  
Charlotte L Bevan
Keyword(s):  
Lipid Metabolism ◽  
Male Fertility ◽  
Reproductive Function ◽  
Normal Male ◽  
Published Data ◽  
Liver X Receptors ◽  
Lipid Disorders ◽  
Male Reproductive Function ◽  
X Receptors ◽  
Lipid Balance

Liver X receptors (LXRs) are ligand-dependent transcription factors acting as ‘cholesterol sensors’ to regulate lipid homeostasis in cells. The two isoforms, LXRα (NR1H3) and LXRβ (NR1H2), are differentially expressed, with the former expressed predominantly in metabolically active tissues and the latter more ubiquitously. Both are activated by oxidised cholesterol metabolites, endogenously produced oxysterols. LXRs have important roles in lipid metabolism and inflammation, plus a number of newly emerging roles. They are implicated in regulating lipid balance in normal male reproductive function and may provide a link between male infertility and lipid disorders and/or obesity. Studies from Lxr knockout mouse models provide compelling evidence to support this. More recently published data suggest distinct and overlapping roles of the LXR isoforms in the testis and recent evidence of a role for LXRs in human male fertility. This review summarises the current literature and explores the likely link between LXR, lipid metabolism and male fertility as part of a special issue on Liver X receptors in International Journal of Molecular Sciences.

scholarly journals Regulation of Cholesterol Homeostasis and Lipid Metabolism in Skeletal Muscle by Liver X Receptors

2002 ◽  
Vol 277 (43) ◽  
pp. 40722-40728 ◽  
Author(s):  
George E. O. Muscat ◽  
Brandee L. Wagner ◽  
Jinzhao Hou ◽  
Rajendra K. Tangirala ◽  
Eric D. Bischoff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Cholesterol Homeostasis ◽  
Liver X Receptors ◽  
X Receptors

Lipid metabolism as a mechanism of immunomodulation in macrophages: the role of liver X receptors

2020 ◽  
Vol 53 ◽  
pp. 18-26 ◽  
Author(s):  
Sophia Leussink ◽  
Irene Aranda-Pardos ◽  
Noelia A-Gonzalez
Keyword(s):  
Lipid Metabolism ◽  
Liver X Receptors ◽  
X Receptors

Liver X receptors and immune regulation

2010 ◽  
Vol 1 (5-6) ◽  
pp. 381-387
Author(s):  
Satoshi Nunomura ◽  
Makoto Makishima ◽  
Chisei Ra
Keyword(s):  
Lipid Metabolism ◽  
Immune Cells ◽  
Immune Regulation ◽  
Cholesterol Synthesis ◽  
Inflammatory Responses ◽  
Liver X Receptors ◽  
Immunoglobulin Production ◽  
Intracellular Cholesterol ◽  
X Receptors ◽  
Derivatives Of

AbstractRecent studies suggest that homeostasis of lipid metabolism is crucial for the function of various immune cells. Oxygenated derivatives of cholesterol (oxysterols) are well-known regulators of lipid metabolism and have diverse functions, such as inhibition of cholesterol synthesis, efflux of intracellular cholesterol, synthesis of cholesterol esters, and activation of liver X receptors (LXRs). In this review, we introduce novel roles of the oxysterol receptors LXRs in the immune system, including regulation of inflammatory responses, T cell expansion, immunoglobulin production, and antitumor responses. We also discuss lipid-mediated signaling as a potential target for treatment of immune diseases.

Reciprocal regulation of inflammation and lipid metabolism by liver X receptors

10.1038/nm820 ◽  
2003 ◽  
Vol 9 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Sean B. Joseph ◽  
Antonio Castrillo ◽  
Bryan A. Laffitte ◽  
David J. Mangelsdorf ◽  
Peter Tontonoz
Keyword(s):  
Lipid Metabolism ◽  
Liver X Receptors ◽  
Reciprocal Regulation ◽  
X Receptors

scholarly journals Activating Signal Cointegrator 2 Required for Liver Lipid Metabolism Mediated by Liver X Receptors in Mice

2003 ◽  
Vol 23 (10) ◽  
pp. 3583-3592 ◽  
Author(s):  
Seung-Whan Kim ◽  
Keunhee Park ◽  
Eunyee Kwak ◽  
Eunho Choi ◽  
Seunghee Lee ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Lipid ◽  
Dominant Negative Effect ◽  
Receptor Interaction ◽  
High Cholesterol Diet ◽  
Liver X Receptors ◽  
Transcriptional Coactivator ◽  
Lxxll Motif ◽  
Liver Lipid Metabolism ◽  
X Receptors

ABSTRACT Activating signal cointegrator 2 (ASC-2), a cancer-amplified transcriptional coactivator of nuclear receptors and many other transcription factors, contains two LXXLL-type nuclear receptor interaction domains. Interestingly, the second LXXLL motif is highly specific to the liver X receptors (LXRs). In cotransfection, DN2, an ASC-2 fragment encompassing this motif, exerts a potent dominant-negative effect on transactivation by LXRs, which is rescued by ectopic coexpression of the full-length ASC-2 but not by other LXXLL-type coactivators, such as SRC-1 and TRAP220. In contrast, DN2/m, in which the LXXLL motif is mutated to LXXAA to abolish the interactions with LXRs, is without any effect. Accordingly, expression of DN2, but not DN2/m, in transgenic mice results in phenotypes that are highly homologous to those previously observed with LXRα−/− mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRα in the liver upon being fed a high-cholesterol diet. These results identify ASC-2 as a physiologically important transcriptional coactivator of LXRs and demonstrate its pivotal role in the liver lipid metabolism.

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