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Vasculature-associated fat macrophages readily adapt to inflammatory and metabolic challenges.

The Journal of experimental medicine (2019-03-14)
Hernandez Moura Silva, André Báfica, Gabriela Flavia Rodrigues-Luiz, Jingyi Chi, Patricia d'Emery Alves Santos, Bernardo S Reis, David P Hoytema van Konijnenburg, Audrey Crane, Raquel Duque Nascimento Arifa, Patricia Martin, Daniel Augusto G B Mendes, Daniel Santos Mansur, Victor J Torres, Ken Cadwell, Paul Cohen, Daniel Mucida, Juan J Lafaille
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Collagenase from Clostridium histolyticum, release of rat epididymal adipocytes and hepatocytes tested (for methodology see Type II and Type IV), Type VIII, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
Giemsa stain, modified
Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Rhodamine B isothiocyanate–Dextran, average mol wt ~70,000
Sigma-Aldrich
Tamoxifen, ≥99%