White adipose tissue (WAT) is increasingly recognized as a highly heterogeneous organ, comprising diverse adipocytes, immune cells, vascular cells, and adipose stromal and progenitor cells (ASPCs), all of which play important roles in regulating tissue function. Although the role of omental fat has been extensively studied, relatively little is known about other visceral depots such as mesenteric, mesocolic, mesorectal, and epiploic fat, which provide mechanical support, metabolic regulation, and immune surveillance of the gastrointestinal tract. Past studies have indicated depot-specific variations, such as smaller mesenteric adipocytes and increased B-cell content over mesocolic fat, and relationships between epiploic WAT and insulin resistance, but these studies have not been associated with high-resolution molecular studies.
To address this gap, researchers profiled abdominal subcutaneous fat and four visceral depots from eight adults (n = 4 men, n = 4 women) undergoing gastric bypass surgery using single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (STx). After quality control, 255,273 nuclei across 34 snRNA-seq samples and 61,560 STx spots across 36 samples were analyzed.
Platform cross-linkage was done with Harmony and scVI, and six major cell types were annotated: ASPCs, mesothelial cells, vascular cells, immune cells, adipocytes, and Schwann cells. In depots, ASPCs were found in 20%-30% of cells, mesothelial in 10%-25% (not in subcutaneous WAT), vascular in 5%-15%, and immune in 30-50% of cells, and adipocytes in 2025%, and Schwann cells <1%. This was determined by comparison to existing datasets, which showed that the adipocytes in this cohort fit the high-BMI profiles, implying that the study represents obesity-related adipose tissue.
Detailed analyses revealed depot-specific heterogeneity within the stromal-vascular compartment. Subcutaneous WAT lacked mesothelial cells and was dominated by APOD⁺ adipose stromal and progenitor cells (ASPCs), vascular endothelial cells, and lipid-associated macrophages. Mesenteric and mesocolic depots resembled each other, and epiploic WAT featured high mesothelial subtype and IGFBP2+ dedicated preadipocyte (CPA), and mesentery WAT exhibited high levels of tissue-resident and recruited myeloid and lymphoid cells, such as T helper 17 and type 2 conventional dendritic cells. Cell2location spatial mapping and a custom cell2location and a homegrown framework (SENSE) identified cellular niches and ASPCs layering. The mesenchymal stem cells that were found are the CD55+ near the mesothelium in the visceral fat and the reticular interstitium rich in connective tissue in the subcutaneous fat. The layers of intermediate and CPA populations were concentric to mature adipocytes, which depicts an adipogenic pathway as identified by pseudo-time analysis.
CellChat analysis of cell-cell communication in epiploic WAT revealed that mesothelial cells, lymphoid cells, and adipocytes were serious signal senders, and signal receivers were vascular cells and mostly myeloid cells. Extracellular matrix remodelling, migration, and inflammatory pathways were also upregulated in this depot. SAA1 and SAA2 were highly induced by LPS and TNF-alpha in adipocytes only, through the NF-KB and STAT3 pathways, which are in line with hypomethylated promoter regions.
Recombinant SAA1 stimulated pro-inflammatory and metabolic responses in adipose-resident myeloid cells, highlighting an adipocyte–immune signaling axis. Collectively, these experiments demonstrate that human WAT depots differ markedly in cellular composition, spatial organization, and intercellular signaling.
The adipose tissue is more structurally regulated than previously believed, with multilayered adipogenic niches and depot-based immune crosstalk, especially in epiploic fat. The results highlight the importance of shifting the focus on omental fat in visceral research and consider it as a resource to conduct future studies on obesity, metabolism, and inflammation.
Reference: Jalkanen J, Zhong J, Nono Nankam PA, et al. Cytoarchitectural multi-depot profiling reveals immune-metabolic crosstalk in human colon-associated adipose tissue. Cell Metab. 2026;38:1-15. doi:10.1016/j.cmet.2025.12.008
