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    Role for Retinoic Acid-Related Orphan Receptor Alpha (RORα) Expressing Macrophages in Diet-Induced Obesity


    Harns, Emily and Roberts, Joseph and Bermingham, Rachel and Hogan, Andrew and O'Shea, Donal and O'Neill, Luke and Fallon, Padraic G. (2020) Role for Retinoic Acid-Related Orphan Receptor Alpha (RORα) Expressing Macrophages in Diet-Induced Obesity. Frontiers in Immunology, 11 (1966). pp. 1-13. ISSN 1664-3224

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    Abstract

    The transcription factor RORα plays an important role in regulating circadian rhythm, inflammation, metabolism, and cellular development. Herein we show a role for RORα-expressing macrophages in the adipose tissue in altering the metabolic state of mice on a high-fat diet. The expression of Rora and RORA is elevated in white adipose tissue from obese mice and humans when compared to lean counterparts. When fed a high-fat diet Rora reporter mice revealed increased expression of Rora-YFP in macrophages in white adipose tissue deposits. To further define the potential role for Rora-expressing macrophages in the generation of an aberrant metabolic state Rorafl/flLysMCre/+ mice, which do not express Rora in myeloid cells, were maintained on a high-fat diet, and metabolic parameters assessed. These mice had significantly impaired weight gain and improved metabolic parameters in comparison to Rorafl/fl control mice. Further analysis of the immune cell populations within white adipose tissue deposits demonstrates a decrease in inflammatory adipose tissue macrophages (ATM). In obese reporter mouse there was increased in Rora-YFP expressing ATM in adipose tissue. Analysis of peritoneal macrophage populations demonstrates that within the peritoneal cavity Rora-expression is limited to myeloid-derived macrophages, suggesting a novel role for RORα in macrophage development and activation, which can impact on metabolism, and inflammation.

    Item Type: Article
    Keywords: RORα; macrophage; inflammation; metabolism; obesity;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 14910
    Identification Number: https://doi.org/10.3389/fimmu.2020.01966
    Depositing User: Andrew Hogan
    Date Deposited: 11 Oct 2021 11:55
    Journal or Publication Title: Frontiers in Immunology
    Publisher: Frontiers Media
    Refereed: Yes
    URI:
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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