T-Cell Signaling Pathways, Including Exhaustion, Predominate in Unhealthy Visceral and Subcutaneous Adipose Tissues

Area of Science:

• Adipose tissue biology
• Immunology
• Metabolic syndrome research

Background:

• Obesity is not a perfect indicator of metabolic health, with visceral adipose tissue (VAT) linked to poor health and subcutaneous adipose tissue (SAT) considered protective.
• A knowledge gap exists regarding the specific and shared functions of SAT and VAT across the metabolic syndrome (MetS) spectrum.

Purpose of the Study:

• To investigate the shared and unique functions of SAT and VAT in the context of metabolic health and syndrome.
• To identify molecular signatures associated with MetS risk in different adipose tissue depots.

Main Methods:

• Quantification of SAT and VAT transcriptomes in a nonhuman primate model of MetS.
• Calculation of quantitative MetS risk scores and application of weighted gene correlation network analysis (WGCNA) to identify relevant transcripts.
• Pathway enrichment analysis to understand the biological processes involved.

Main Results:

• Both SAT and VAT showed convergence on T-cell signaling pathways, notably T-cell exhaustion.
• VAT-unique pathways involved interferon signaling and immune crosstalk, while SAT-unique pathways focused on innate immune cell signaling and vascular involvement.
• Despite molecular signatures, T-cell abundance in VAT did not correlate with MetS scores.

Conclusions:

• T-cell signaling and exhaustion are predominant in metabolically unhealthy SAT and VAT.
• The study provides novel insights into adipose depot-specific responses and T-cell biology using advanced transcriptomic analysis and continuous MetS scoring.