Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes

OBJECTIVE—To establish the mechanism of the phenotypic switch of adipose tissue macrophages (ATMs) from an alterna-tively activated (M2a) to a classically activated (M1) phenotype with obesity. RESEARCH DESIGN AND METHODS—ATMs from lean and obese (high-fat diet–fed) C57Bl/6 mice were analyzed by a combination of flow cytometry, immunofluorescence, and ex-pression analysis for M2a and M1 genes. Pulse labeling of ATMs with PKH26 assessed the recruitment rate of ATMs to spatially distinct regions. RESULTS—Resident ATMs in lean mice express the M2a marker macrophage galactose N-acetyl-galactosamine specific lectin 1 (MGL1) and localize to interstitial spaces between adipocytes independent of CCR2 and CCL2. With diet-induced obesity, MGL1 ATMs remain in interstitial spaces, whereas