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.

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 The NLRP3 Inflammasome as a Novel Player of the Intercellular Crosstalk in Metabolic Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Elisa Benetti ◽  
Fausto Chiazza ◽  
Nimesh S. A. Patel ◽  
Massimo Collino
Keyword(s):  
Chronic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Inflammasome Activation ◽  
Nucleotide Binding Domain ◽  
Metabolic Inflammation ◽  
Nlrp3 Inflammasome Activation ◽  
Leucine Rich Repeat Protein

The combination of obesity and type 2 diabetes is a serious health problem, which is projected to afflict 300 million people worldwide by 2020. Both clinical and translational laboratory studies have demonstrated that chronic inflammation is associated with obesity and obesity-related conditions such as insulin resistance. However, the precise etiopathogenetic mechanisms linking obesity to diabetes remain to be elucidated, and the pathways that mediate this phenomenon are not fully characterized. One of the most recently identified signaling pathways, whose activation seems to affect many metabolic disorders, is the “inflammasome,” a multiprotein complex composed of NLRP3 (nucleotide-binding domain and leucine-rich repeat protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and procaspase-1. NLRP3 inflammasome activation leads to the processing and secretion of the proinflammatory cytokines interleukin- (IL-) 1βand IL-18. The goal of this paper is to review new insights on the effects of the NLRP3 inflammasome activation in the complex mechanisms of crosstalk between different organs, for a better understanding of the role of chronic inflammation in metabolic disease pathogenesis. We will provide here a perspective on the current research on NLRP3 inflammasome, which may represent an innovative therapeutic target to reverse the detrimental metabolic consequences of the metabolic inflammation.

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.

scholarly journals Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

2022 ◽  
Vol 12 ◽  
Author(s):  
Jianglian She ◽  
Tanwei Gu ◽  
Xiaoyan Pang ◽  
Yonghong Liu ◽  
Lan Tang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Natural Products ◽  
Nuclear Receptors ◽  
Farnesoid X Receptor ◽  
Liver X Receptors ◽  
Terrestrial Plants ◽  
Comprehensive Overview ◽  
Chemical Structures ◽  
Bioactive Properties ◽  
X Receptors

Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000–2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion.

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

Potential role of rituximab in metastatic castrate-resistant prostate cancer

2018 ◽  
Vol 25 (6) ◽  
pp. 1509-1511 ◽  
Author(s):  
Poorva Bindal ◽  
Sharif AA Jalil ◽  
Lisa M Holle ◽  
Jessica M Clement
Keyword(s):  
Prostate Cancer ◽  
B Cell ◽  
Disease Progression ◽  
Androgen Deprivation ◽  
Cell Infiltration ◽  
Prostate Cells ◽  
Develop Disease Progression ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

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

scholarly journals Liver X Receptors and Their Implications in the Physiology and Pathology of the Peripheral Nervous System

2019 ◽  
Vol 20 (17) ◽  
pp. 4192
Author(s):  
Venkat Krishnan Sundaram ◽  
Charbel Massaad ◽  
Julien Grenier
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Peripheral Nerves ◽  
Therapeutic Potential ◽  
Positive Impact ◽  
Redox Homeostasis ◽  
Liver X Receptors ◽  
X Receptors

Recent research in the last decade has sought to explore the role and therapeutic potential of Liver X Receptors (LXRs) in the physiology and pathologies of the Peripheral Nervous System. LXRs have been shown to be important in maintaining the redox homeostasis in peripheral nerves for proper myelination, and they regulate ER stress in sensory neurons. Furthermore, LXR stimulation has a positive impact on abrogating the effects of diabetic peripheral neuropathy and obesity-induced allodynia in the Peripheral Nervous System (PNS). This review details these findings and addresses certain important questions that are yet to be answered. The potential roles of LXRs in different cells of the PNS are speculated based on existing knowledge. The review also aims to provide important perspectives for further research in elucidating the role of LXRs and assessing the potential of LXR based therapies to combat pathologies of the Peripheral Nervous System.

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