Abstract
The activation of adipose tissue macrophages (ATMs) in obesity is a key mediator of metabolic complications. Therefore, deciphering the cellular and molecular mechanisms initiating ATM activation could reveal regulatory pathways important to prevent obesity‐associated metabolic disorders. While stressed or dying adipocytes have been described as the source of factors activating ATMs, herein we discovered that endothelial cells directly communicate with a distinct population of ATMs to induce their transcriptional reprogramming in response to obesity in mice and humans. CD200R expressed by these perivascular ATMs regulated the acquisition of unique properties shaped by the obese adipose tissue vasculature. Systems biology and ATM-specific silencing in obese mice revealed a unique downstream signaling whereby CD200R act as a rheostat controlling multiple functions of ATMs. Together, these studies provide evidence for a CD200-CD200R axis triggering the reprogramming of ATMs by endothelial cells in obesity.
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