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

Front Immunol. 2020 Aug 27:11:1966. doi: 10.3389/fimmu.2020.01966. eCollection 2020.

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.

Keywords: RORα; inflammation; macrophage; metabolism; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Biomarkers
  • Diet*
  • Diet, High-Fat
  • Disease Models, Animal
  • Energy Metabolism
  • Flow Cytometry
  • Gene Expression*
  • Humans
  • Macrophages / metabolism*
  • Mice
  • Mice, Transgenic
  • Monocytes / immunology
  • Monocytes / metabolism
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Obesity / etiology*
  • Obesity / metabolism*
  • Obesity / pathology
  • Retinoic Acid Receptor alpha / genetics*
  • Retinoic Acid Receptor alpha / metabolism
  • Stress, Physiological
  • Stromal Cells / metabolism

Substances

  • Biomarkers
  • Retinoic Acid Receptor alpha