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Biomolecules
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Advances in Liver X Receptors
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Advances in Liver X Receptors

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 4545

Special Issue Editors

Dr. Kaori Endo-Umeda

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Guest Editor
Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
Interests: nuclear receptors; lipid metabolism; cholesterol; inflammation; tissue-resident immune cells; non-alcohol steatohepatitis; atherosclerosis; tumor immunity
Prof. Dr. Makoto Makishima

E-Mail Website
Guest Editor
Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
Interests: regulation of lipid metabolism and immunity by nuclear receptors in the liver and intestine; molecular basis of function-selective nuclear receptor ligands and application to drug discovery; regulation of xenobiotic metabolisms and their relationship to human disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The nuclear receptor liver X receptors α (LXRα) and LXRβ are transcription factors activated by oxysterols and regulate cholesterol homeostasis. LXRs also play important roles in the regulation of innate and adaptive immune responses in leukocytes. Thus, LXRs could be therapeutic targets for various diseases such as cardiovascular diseases, non-alcoholic steatohepatitis, cancer, infectious diseases and autoimmune diseases. However, their cell-type specific target genes and functions have not completely been explored.

This Special Issue welcomes original articles and reviews focused on the recent advances in the regulation of metabolism and immunity by LXRs in physiological and disease conditions. We also welcome articles regarding other novel LXR functions and the development of novel LXR ligands for protection and therapy in relation to disease treatment.

We look forward to reading your contributions.

Dr. Kaori Endo-Umeda
Prof. Dr. Makoto Makishima
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liver X receptor
  • lipid metabolism
  • cholesterol
  • oxysterol
  • atherosclerosis
  • non-alcoholic steatohepatitis
  • inflammation
  • tumor immunity

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Published Papers (3 papers)

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Review

30 pages, 2591 KiB  
Review
Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis
by Kaori Endo-Umeda and Makoto Makishima
Biomolecules 2025, 15(4), 579; https://doi.org/10.3390/biom15040579 - 14 Apr 2025
Viewed by 348
Abstract
Hypercholesterolemia causes atherosclerosis by inducing immune cell migration and chronic inflammation in arterial walls. Recent single-cell analyses reveal the presence of lipid-enriched foamy macrophages, as well as other macrophage subtypes, neutrophils, T cells, and B cells, in atherosclerotic plaques in both animal models [...] Read more.
Hypercholesterolemia causes atherosclerosis by inducing immune cell migration and chronic inflammation in arterial walls. Recent single-cell analyses reveal the presence of lipid-enriched foamy macrophages, as well as other macrophage subtypes, neutrophils, T cells, and B cells, in atherosclerotic plaques in both animal models and humans. These cells interact with each other and other cells, including non-immune cells such as endothelial cells and smooth muscle cells. They thereby regulate metabolic, inflammatory, phagocytic, and cell death processes, thus affecting the progression and stability of atherosclerotic plaques. The nuclear receptors liver X receptor (LXR)α and LXRβ are transcription factors that are activated by oxysterols and regulate lipid metabolism and immune responses. LXRs regulate cholesterol homeostasis by controlling cholesterol’s transport, absorption, synthesis, and breakdown in the liver and intestine. LXRs are also highly expressed in tissue-resident and monocyte-derived macrophages and other immune cells, including both myeloid cells and lymphocytes, and they regulate both innate and adaptive immune responses. Interestingly, LXRs have immunosuppressive and immunoregulatory functions that are cell-type-dependent. In animal models of atherosclerosis, LXRs have been shown to be involved in both progression and regression phases. The pharmacological activation of LXR enhances cholesterol efflux from macrophages and promotes atherosclerosis progression. Deleting LXR in immune cells, especially myeloid cells, accelerates atherosclerosis by increasing monocyte migration, macrophage proliferation and activation, and neutrophil extracellular traps (NETs); furthermore, the deletion of hematopoietic LXRs impairs the regression of atherosclerotic plaques. Therefore, LXRs in immune cells may be a potent therapeutic target for atherosclerosis. Full article
(This article belongs to the Special Issue Advances in Liver X Receptors)
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17 pages, 3105 KiB  
Review
The Liver X Receptor Promotes Immune Homeostasis via Controlled Activation of the Innate Immune System in the Liver
by Hiroyuki Nakashima, Bradley M. Kearney and Manabu Kinoshita
Biomolecules 2025, 15(1), 25; https://doi.org/10.3390/biom15010025 - 28 Dec 2024
Viewed by 1231
Abstract
The liver is an indispensable metabolic organ, responsible for accumulating and transporting various nutritional compounds in hepatocytes. However, the transport of these materials from the liver is an energetically intensive task because they contain a considerable number of hydrophobic components, including free cholesterol, [...] Read more.
The liver is an indispensable metabolic organ, responsible for accumulating and transporting various nutritional compounds in hepatocytes. However, the transport of these materials from the liver is an energetically intensive task because they contain a considerable number of hydrophobic components, including free cholesterol, and require specialized transfer proteins to shuttle these substances through an aqueous phase. Liver X receptors (LXRs) induce the expression of cholesterol transporters in macrophages to transport free cholesterol derived from apoptotic cells into extracellular space via high-density lipoproteins. Additionally, LXRs control innate immune cells through two major mechanisms: upregulating the phagocytic activity of macrophages and suppressing inflammatory reactions to prevent aggressive activation of immune cells. Therefore, the primary role of LXRs is to accelerate efferocytosis without provoking inflammation and facilitate the transfer of free cholesterol from the intracellular space. This mechanism makes the innate immune system a substantial contributor to systemic metabolic control. Concomitantly, LXRs are important factors in regulating systemic defense mechanisms through the efficient regulation of immune cells. LXR activation, therefore, has great potential for clinical applications in the treatment of metabolic, infectious, and autoimmune diseases. In this review, we discuss the current understanding of the link between LXRs and innate immune cells in the liver, along with prospects for clinical applications of LXR agonists. Full article
(This article belongs to the Special Issue Advances in Liver X Receptors)
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16 pages, 1606 KiB  
Review
Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers
by Ning Han, Man Yuan, Libo Yan and Hong Tang
Biomolecules 2023, 13(8), 1184; https://doi.org/10.3390/biom13081184 - 28 Jul 2023
Cited by 7 | Viewed by 2432
Abstract
Liver X receptor α (LXRα), a member of the nuclear receptor superfamily, is identified as a protein activated by ligands that interacts with the promoters of specific genes. It regulates cholesterol, bile acid, and lipid metabolism in normal physiological processes, and it participates [...] Read more.
Liver X receptor α (LXRα), a member of the nuclear receptor superfamily, is identified as a protein activated by ligands that interacts with the promoters of specific genes. It regulates cholesterol, bile acid, and lipid metabolism in normal physiological processes, and it participates in the development of some related diseases. However, many studies have demonstrated that LXRα is also involved in regulating numerous human malignancies. Aberrant LXRα expression is emerging as a fundamental and pivotal factor in cancer cell proliferation, invasion, apoptosis, and metastasis. Herein, we outline the expression levels of LXRα between tumor tissues and normal tissues via the Oncomine and Tumor Immune Estimation Resource (TIMER) 2.0 databases; summarize emerging insights into the roles of LXRα in the development, progression, and treatment of different human cancers and their diversified mechanisms; and highlight that LXRα can be a biomarker and therapeutic target in diverse cancers. Full article
(This article belongs to the Special Issue Advances in Liver X Receptors)
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