Cytoarchitectural multi-depot profiling reveals immune-metabolic crosstalk in human colon-associated adipose tissue.

While it is well established that the cellular composition of white adipose tissue (WAT) varies between depots, the functional relevance of this heterogeneity remains unclear. By combining spatial and single-nucleus RNA sequencing, we provide a comprehensive map of subcutaneous and visceral (omental, mesenteric, mesocolic, and epiploic) WAT in both men and women. Our analyses reveal shared features, such as the spatial organization of adipogenesis, alongside depot-specific characteristics, including distinct cell-type enrichments and unique cell-cell communication routes. Epiploic WAT stands out by harboring high proportions of serum amyloid A expressing fat cells (encoded by SAA1/SAA2) and several leukocyte populations. Through mechanistic studies, we demonstrate that adipocyte SAA1/SAA2 expression is induced by inflammatory signals, including lipopolysaccharide, and that SAA1 activates immune responses in adipose-resident myeloid cells. Collectively, our findings suggest that visceral WAT exhibits distinct cytoarchitectural properties, with those located near the colon adapting by developing specialized adipocytes and immune cell populations.