Distinct T Cell Subset Profiles and T-Cell Receptor Signatures in Metabolically Unhealthy Obesity.

Area of Science:

• Immunology
• Metabolic Health
• Obesity Research

Background:

• Metabolically unhealthy obesity (MUO) is linked to inflammation and metabolic disorders, unlike metabolically healthy obesity (MHO).
• T cell dysregulation in blood and adipose tissue may drive obesity-related metabolic dysfunction.
• Specific T cell subset profiles and T-cell receptor (TCR) repertoires in MHO vs. MUO are not well understood.

Purpose of the Study:

• To characterize T cell subset profiles and TCR repertoires in peripheral blood and omental adipose tissue (oAT) of MHO and MUO individuals.
• To identify potential immune biomarkers differentiating MHO from MUO.

Main Methods:

• Analysis of T cell subsets and TCR repertoires using flow cytometry and high-throughput TCR sequencing.
• Comparison between age- and BMI-matched MHO and MUO individuals.
• Examination of both peripheral blood and omental adipose tissue (oAT).

Main Results:

• MUO individuals showed higher proportions of memory CD4+ T cells, including central memory T cells, in blood and oAT.
• Circulating CD8+ T cells were elevated in MUO, but subset composition was similar in blood and oAT.
• oAT TCR repertoires were more restricted and skewed in MUO, with specific TRB V gene amplification and altered CDR3 length.

Conclusions:

• Distinct CD4+ T cell populations and TCR signatures are associated with metabolically unhealthy obesity.
• These immune profiles may serve as potential biomarkers for metabolic dysfunction in obesity.
• Findings offer insights into immune mechanisms driving the transition from MHO to MUO.