Human deep subcutaneous adipose tissue is enriched for inflammatory and tissue remodeling pathways

Area of Science:

• Adipose tissue biology
• Transcriptomics
• Immunology

Background:

• Subcutaneous superficial adipose tissue (SAT) and deep adipose tissue (DAT) are anatomically distinct fat depots.
• Previous research suggests functional and histological differences between SAT and DAT.
• The molecular mechanisms underlying these differences remain incompletely understood.

Purpose of the Study:

• To perform a comprehensive transcriptomic comparison between SAT and DAT.
• To identify distinct cellular compositions and molecular pathways in SAT versus DAT.
• To elucidate the functional implications of these differences in adipose tissue biology.

Main Methods:

• Bulk RNA sequencing of SAT and DAT.
• Single-cell RNA sequencing of SAT and DAT.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
• Analysis of gene expression in specific cell types, including macrophages and fibroblasts.

Main Results:

• Bulk RNA sequencing revealed DAT is enriched in genes associated with inflammation, tissue remodeling, and oxidative stress.
• Pathway analyses indicated significant enrichment of inflammatory response, cytokine signaling, and TNF signaling in DAT.
• Single-cell RNA sequencing identified distinct immune and stromal cell compositions, with DAT showing increased Mox macrophages and specific fibroblasts/preadipocytes, while SAT had more M2 macrophages and CD8/NK cells.

Conclusions:

• DAT exhibits a pro-inflammatory and remodeling-prone environment compared to SAT.
• Distinct cellular phenotypes, including stress-responsive fibroblasts (FAPs) and upregulated APOE in DAT macrophages, contribute to depot-specific functions.
• These findings highlight significant cellular and molecular heterogeneity between SAT and DAT, implicating DAT in more active inflammatory and remodeling processes.