scholarly journals Minireview: Liver X Receptor β: Emerging Roles in Physiology and Diseases

2009 ◽  
Vol 23 (2) ◽  
pp. 129-136 ◽  
Author(s):  
Chiara Gabbi ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Current Knowledge ◽  
Large Family ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Liver X Receptors ◽  
Cholesterol Accumulation ◽  
Reverse Transport ◽  
X Receptors ◽  
Lateral Sclerosis

Abstract Liver X receptors, LXRα and LXRβ, are nuclear receptors belonging to the large family of transcription factors. After activation by oxysterols, LXRs play a central role in the control of lipid and carbohydrate metabolism as well as inflammation. The role of LXRα has been extensively studied, particularly in the liver and macrophages. In the liver it prevents cholesterol accumulation by increasing bile acid synthesis and secretion into the bile through ATP-binding cassette G5/G8 transporters, whereas in macrophages it increases cholesterol reverse transport. The function of LXRβ is still under investigation with most of the current knowledge coming from the study of phenotypes of LXRβ−/− mice. With these mice new emerging roles for LXRβ have been demonstrated in the pathogenesis of diseases such as amyotrophic lateral sclerosis and chronic pancreatitis. The present review will focus on the abnormalities described so far in LXRβ−/− mice and the insight gained into the possible roles of LXRβ in human diseases.

Using integrative lipid systems biology to understand the role of Liver X receptors (LXRs) in male reproduction

2018 ◽  
Author(s):  
Sheba Jarvis ◽  
Lee Gethings ◽  
Raffaella Gadeleta ◽  
Emmanuelle Claude ◽  
Robert Winston ◽  
...  
Keyword(s):  
Systems Biology ◽  
Male Reproduction ◽  
Liver X Receptors ◽  
X Receptors

scholarly journals Recombinant 2-enoyl-CoA hydratase derived from rat peroxisomal multifunctional enzyme 2: role of the hydratase reaction in bile acid synthesis

1997 ◽  
Vol 328 (2) ◽  
pp. 377-382 ◽  
Author(s):  
Yong-Mei QIN ◽  
M. Antti HAAPALAINEN ◽  
Demara CONRY ◽  
A. Dean CUEBAS ◽  
J. Kalervo HILTUNEN ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Hydration Reaction ◽  
Multifunctional Enzymes ◽  
Hydratase Activity ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Liver Peroxisomes ◽  
Enoyl Coa Hydratase

Rat liver peroxisomes contain two multifunctional enzymes: (1) perMFE-1 [2-enoyl-CoA hydratase 1/Δ3,Δ2-enoyl-CoA isomerase/(S)-3-hydroxyacyl-CoA dehydrogenase] and (2) perMFE-2 [2-enoyl-CoA hydratase 2/(R)-3-hydroxyacyl-CoA dehydrogenase]. To investigate the role of the hydratase activity of perMFE-2 in β-oxidation, a truncated version of perMFE-2 was expressed in Escherichia coli as a recombinant protein. The protein catalyses the hydration of straight-chain (2E)-enoyl-CoAs to (3R)-hydroxyacyl-CoAs, but it is devoid of hydratase 1 [(2E)-enoyl-CoA to (3S)-hydroxyacyl-CoA] and (3R)-hydroxyacyl-CoA dehydrogenase activities. The purified enzyme (46 kDa hydratase 2) can be stored as an active enzyme for at least half a year. The recombinant enzyme hydrates (24E)-3α,7α,12α-trihydroxy- 5β-cholest-24-enoyl-CoA to (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestanoyl-CoA, which has previously been characterized as a physiological intermediate in bile acid synthesis. The stereochemistry of the products indicates that the hydration reaction catalysed by the enzyme proceeds via a syn mechanism. A monofunctional 2-enoyl-CoA hydratase 2 has not been observed as a wild-type protein. The recombinant 46 kDa hydratase 2 described here survives in a purified form under storage, thus being the first protein of this type amenable to application as a tool in metabolic studies.

scholarly journals Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000948
Author(s):  
Laura Bousset ◽  
Amandine Septier ◽  
Julio Bunay ◽  
Allison Voisin ◽  
Rachel Guiton ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Nuclear Receptors ◽  
Metabolic Disorders ◽  
Androgen Deprivation ◽  
Liver X Receptors ◽  
Phenotypic Alteration ◽  
Prostate Cells ◽  
Common Causes ◽  
X Receptors

Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.

scholarly journals MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs

2020 ◽  
Vol 21 (6) ◽  
pp. 2229 ◽  
Author(s):  
Monika M. Kaczmarek ◽  
Joanna Najmula ◽  
Maria M. Guzewska ◽  
Emilia Przygrodzka
Keyword(s):  
Current Knowledge ◽  
Mammalian Species ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Large Family ◽  
Protein Coding ◽  
The Past ◽  
Domestic Livestock ◽  
Implantation Period

MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk.

Elucidating the role of Liver X receptors (LXRs) in the testis using lipid systems biology

2017 ◽  
Author(s):  
Sheba Jarvis ◽  
Lee Gethings ◽  
Raffaella Gadaleta ◽  
Lord Robert Winston ◽  
Catherine Williamson ◽  
...  
Keyword(s):  
Systems Biology ◽  
Liver X Receptors ◽  
X Receptors

Role of the nuclear orphan receptor Rev-erb??; in the regulation of bile acid synthesis

2006 ◽  
Vol 18 (1) ◽  
pp. A44
Author(s):  
T Claudel ◽  
H Duez ◽  
J van der Veen ◽  
C Fontaine ◽  
R Havinga ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Orphan Receptor ◽  
Nuclear Orphan Receptor
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