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.
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