Classical Macrophage Activation Decreases The Level Of Extracellular Microrna-223 Secreted By Bone-Marrow-Derived Macrophage

Compelling evidence demonstrated that adipose‐tissue‐resident macrophages (ATMs) are critical educators in adipose tissue niche by regulating adipocyte functions. ATMs in obese objects primarily display a classical activation status with pro‐inflammatory features (M1), which is a major shift from ATMs in lean adipose tissues that exhibit mainly anti‐inflammatory profiles (M2). As the major cell compartment in adipose stroma, ATMs exert profound regulatory effects by secreting large amount of molecules upon environmental cues, including various cytokines and chemokines. Recent study suggested that, in addition to protein and peptide molecules, RNAs can also be detected in the extracellular fluid and may function as a new type of cell communicating molecules. However, why these exRNAs are produced and how they function are yet to be determined. To better understand the regulatory mechanism of ATMs on adipose tissue function, we generated exRNA profiles from the conditioned medium from M1 and M2 macrophages. Interestingly, our results revealed that exRNA profiles are distinct from intracellular RNAs. This evidence supports that exRNAs secretion is a novel marker of macrophage secretion. In conclusion, our study provides the first sets of evidence to support that ATMs can regulate adipose tissue function by actively releasing exRNAs acting in a paracrine manner in the context of obesity‐associated metabolic syndromes.