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

ABSTRACT: The transcription factor ROR? plays an important role in regulating circadian rhythm, inflammation, metabolism, and cellular development. Herein we show a role for ROR?-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/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 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 ROR? in macrophage development and activation, which can impact on metabolism, and inflammation.

SUBMITTER: Hams E 

PROVIDER: S-EPMC7482427 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature