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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  Rora  fl/fl LysM Cre/+  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  Rora  fl/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.

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