Adipose tissue macrophages are found in anatomically distinct subtissular niches, but how different macrophage subsets contribute to adipose tissue function is unclear. In Science, Yu et al. define macrophage populations in adipose tissue and describe a population of macrophages that controls the differentiation of adipocyte stem cells (ASCs) into white adipocytes. Three subsets of macrophages in mouse white adipose tissue were identified with different subtissular localization. CD209b+ macrophages were embryonically derived and found along the septa, the compartment that contains and supports adipocytes, in close proximity to CD26+ ASCs. In response to a high-fat diet, CD209b+ macrophages remained in the septa with limited monocyte recruitment. Depletion of CD209b+ macrophages during a high-fat diet protected mice from weight gain, glucose intolerance and insulin resistance, reduced the number of CD26+ ASCs but increased their expression of genes associated with thermogenesis and beiging. Deletion of Tgfb1 in macrophages recapitulated the phenotype observed in mice depleted of CD209b+ macrophages. CD26+ ASCs from TGFβ1-deficient mice had impaired white adipogenic differentiation and increased thermogenic activity. In humans, septal LYVE1+ adipose tissue macrophages that expressed TGFB1 were found in close association with CD26+ ASCs. Taken together, the authors suggest that CD206b+ adipose tissue macrophages in the septa promote the differentiation of ASCs to white adipocytes, limiting their thermogenic properties.
Original reference: Science 389, eadg1128 (2025)
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