Tissue-resident macrophages are the

Tissue-resident macrophages are the most abundant immune cell population in healthy adipose tissue. Adipose tissuemacrophages (ATMs) change during metabolic stress and are thought to contribute to metabolic syndrome. Here, we studiedATM subpopulations in steady state and in response to nutritional and infectious challenges. We found that tissue-residentmacrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying very highendocytic capacity. We refer to these cells as vasculature-associated ATMs (VAMs). Chronic high-fat diet (HFD) results in theaccumulation of a monocyte-derived CD11c+CD64+ double-positive (DP) macrophage eWAT population with a predominantanti-inflammatory/detoxifying gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads toVAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boostsDP macrophage accumulation. Our results indicate that ATM populations dynamically adapt to metabolic stress andinflammation, suggesting an important role for these cells in maintaining tissue homeostasis.